Term
| What is a Satellite virus? What is an example? |
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Definition
"defective viruses" that require another virus to replicate
DELTA AGENT IN VIRAL HEPATITIS |
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Term
| What are Prions? What type of genome do they have? What are some examples? |
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Definition
| infectious proteins that cause disease and DO NOT CONTAIN ANY NUCLEIC ACID EX: scrapie, mad cow disease, possibly alzheimers |
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Term
| Definition of a conventional Virus |
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Definition
| nucleic acid genome protected by a protein coat |
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Term
|
Definition
| Morphologically complete (potentially infectious) virus |
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Term
|
Definition
nucleic acid-protein complex (genome +shell)
NAKED VIRUSES: don't have lipid envelope and nucleocapsid is the infectious form (virion) |
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Term
| Define Naked Virus. What are examples? |
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Definition
don't have lipid envelope and nucleocapsid is the infectious form (virion)
Ex. Adenoviruses, picornaviruses |
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Term
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Definition
nucleic acid genome and its associated proteins that reside w/in capsid.
some retroviruses don't have a capsid so structure that contains RNA genome is the core |
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Term
| What are some types of viral genomes? |
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Definition
| DNA/RNA; single/double stranded |
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Term
|
Definition
protein coat of a virus W/O GENOME protects the nucleic acid genome
(if there was a genome attached it would be a nucleocapsid) |
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Term
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Definition
repetitive subunits of viral capsids
Can have Single protein or several proteins |
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Term
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Definition
| protein subunit of a capsomere |
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Term
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Definition
| Lipid bilayer membrane that comes from host cell membrane Ex. In herpes comes from cytoplasmic vesicles |
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Term
| What is the Matrix/Tegument |
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Definition
| amorphous protein that has substance found btwn nucleocapsid and envelope |
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Term
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Definition
| Glycoprotein spikes that are inserted into viral envelopes. Act as R. |
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Term
| What is the Cytopathic effect (CPE)? |
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Definition
| Quantitative assay: visible degeneration of cultured cells/ cells in tissue sections caused by viral infection Ex. Owl Eye nuclei in cytomegalovirus infection |
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Term
| What are Plaque Forming Units? |
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Definition
Quantitative assay: area of lysis caused by virus infection of a cell monolayer ex. herpes viruses, adenoviruses, and picornavirus)
Remember this one = only one that's important! |
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Term
| Define hemagglutination? Example of virus you could use this with? |
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Definition
Quantitative assay: ability of certain viruses to crosslink RBC
Doesn't measure infectious virus but the total number of virions in the stock Like bacterial hemagglutinins
Ex. cold agglutination w/ Influenza |
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Term
| Describe focus forming assay |
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Definition
Quantitavie assay change in appearance of a cell monolayer induced by non-lytic/transforming virus Ex. Transforming retroviruses - flip side of PFU
(not thatimportant) |
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Term
| What does infectious dose 50% (ID50) tell you? |
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Definition
Quantitative assay amount of virus stock needed to infect host 50% of the time
(not thatimp) |
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Term
| What do Direct particle counts tell you? |
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Definition
| Quantitative assay (not that important) EM of viral stock. measures total virions not just infectious virus. |
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Term
| In general what does the attachment/adsorption of viruses entail?. Are they infectious at this point? |
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Definition
| initial interaction of virus w/ cell (lock and key mechanism) INFECTIOUS |
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Term
| In general what does the penetration/entry of virus infectious of viruses entail?. Are they infectious at this point? |
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Definition
| transport of virus into cell's interior direct fusion (enveloped) or R med endo INFECTIOUS |
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Term
| In general what does the viral uncoating of viruses entail? Are they infectious at this point? |
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Definition
conformational change in virus structure causing genome to be available. Acidification of endosome causes lipid layer and viral proteins to fall apart.
NOT INFECTIOUS = beginning of eclipse period |
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Term
| In general what does the viral transcription of viruses entail? Are they infectious at this point? |
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Definition
All DNA (except POX) use RNA Pol II to transcribe genes Cascade Regulation w/ immediate early, early and late genes.
NOT INFECTIOUS |
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Term
| What are the 3 steps of Cascade regulation? |
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Definition
immediate early: modify host, upreg other viral genes and downregulate themselves
Early: replicate genome, regulate other genes
Late: make structural components |
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Term
In general what does the viral translation entail? Are they infectious at this point?
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Definition
| Selectively translate viral messages. Posttranslational modification of viral gene products NOT INFECTIOUS |
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Term
| In general what does the viral genome replication entail? Are they infectious at this point? |
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Definition
Use host/viral replication machinery
end problem: Telomerase uses RNA template to make multimers of single repetitive sequence at the ends of chromosomes. All linear DNA viruses (except POX!) have repeats at end of genome |
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Term
| In general what does viral Assembly and morphogenesis entail? Are they infectious at this point? |
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Definition
| All DNA viruses (except POX and HBV) assemble nucleocapsids in nucleus of infected cell Final maturation: enveloped viruses at lipid membrane of cell that can be nuclear or cytoplasmic INFECTIOUS |
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Term
| In general what does the Viral Exit/Release entail? Are they infectious at this point? |
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Definition
| Cell lysis and release of new viral particles or budding of enveloped viruses Infectious |
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Term
| What is the major structural determinant of the mode of viral transmission? |
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Definition
Presence or abscence of an envelope. Enveloped viruses = extremely fragile, spread in resp. droplets, mucus, saliva, blood/semen, injection, organ transplant
non-enveloped viruses = withstand detergents, etc and are FECAL-ORAL and resp routes transmission via fomites |
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Term
| GI transmission is limited to what types of viruses? |
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Definition
| NON-ENVELOPED. Must withstand stomach acidity, bile salts that destroy viral lipid envelopes. Proteolysis of capsid components sometimes needed. |
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Term
| Examples of localized infections |
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Definition
Respiratory: influenza, RSV, rhinovirus
Enteric: rotavirus, norovirus
Skin: HPV (warts) |
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Term
| Describe difference btwn primary and secondary viremia |
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Definition
Primary viremia: few virions in blood that spread to sites
Secondary: virions are released in high levels blood |
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Term
| Example of viruses that use neural spread |
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Definition
| Rabies, Herpes simplex, Varicella Zoster Virus |
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
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Term
| Define abortive infection |
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Definition
| Failed infection. Viruses DO NOT multiply and disappear |
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Term
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Definition
Rapid production of infectious virions, rapid resolution and elimination via adaptive immune system.
Associated w/ RNA viruses
Frequently asymptomatic to maintain in population
Ex: rhinovirus, influenza virus |
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Term
| Define chronic infections |
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Definition
Continuous production/shedding of virus for prolonged periods of time
Slow release of virions w/o killing host cells.
Associated w/ DNA virus
MAJOR RESERVOIR OF VIRIONS
Ex. Hep B virus |
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Term
|
Definition
maintenance of viral genome in host cells in absence of production of infectious virus
DNA viruses/retroviruses
Can be extra-chromosomal/integrated into host w/ reactivation
Ex. HSV1, VZV |
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Term
| Innate immune responses include... |
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Definition
| fever, INF, cytokines, complement, dendritic cells, macs, NK cells |
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Term
| IFN alpha/beta vs IFN gamma |
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Definition
alpha/beta are early defense against viral infection b/c activate target cell antiviral defense to stop viral replication, activate immune response and enhance T cell recognition of infected host cells.
IFN cause the systemic symptoms of lots of infections
Gamma is for macs. not that imp here. |
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Term
| What types of viruses are susceptible to humoral responses? |
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Definition
Ab work on EC viruses while CMI is important for virus-producing cells
IgM to detect disease; IgG to monitor |
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Term
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Definition
small infectious agents that consist of protein but lack nucleic acid
host protein (PrP) turns into infectious agent (PrPsc)w/ accumulation of abnormal isoforms of PrP
progressive, degenerative neurologic disease with a long incubation period
no antigenicity, no inflammation, no immune response and no interferon production. |
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Term
| What is the gold standard for virus identification? |
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Definition
| Tissue culture b/c it is open-ended. PCR looks for a specific agent. |
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Term
| Describe the classification scheme for herpesviruses |
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Definition
Alpha: HSV1, HSV2, VZV
Gamma: EBV, HHV8 (KSAV)
Beta: CMV, HHV6, HHV7 |
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Term
| how is HSV1/2 transmitted? |
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Definition
| Primary infection is contracted through DIRECT CONTACT from a person that is shedding HSV in saliva, urine, genital tract secretions or vesicular fluid |
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Term
| Where does HSV1/2 replicate during the primary infection? |
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Definition
| EPITHELIUM of mucus membranes or skin |
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Term
| Describe latency of HSV1/2 |
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Definition
Virus is transported retrograde by axonal flow and latently is an episome in:
HSV1: TRIGEMINAL
HSV2: SACRAL GANGLIA
Expression of novel RNA latency associated transcripts (LATS)that are optimized for ganglion that they infect |
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Term
| Describe reactivation of HSV1/2 |
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Definition
Virus is transported down axon causing recurrent epithelial infection w/ local spread.
more extensive if T cell deficiency and in eczema. |
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Term
| Describe how HSV1/2 evade the immune system. |
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Definition
Cell-Cell spread that makes syncitial cells. CMI is more critical for resolution but it causes tissue injury.
Control of both the acute and reactivated disease requires both humoral responses that target the viral envelope glycoproteins and CMI |
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Term
| Gross and microscopic pathology of HSV1/2 |
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Definition
Gross: vesicles (skin or mucosa) that ulcerate
Micro: vesicle is intraepithelial and contains cells w/ "type A" intranuclear inclusions w/ eosinophilic dense inclusion surrounded by halo.
often multinucleated cells.
W/ cell lysis maybe initial surrounding neutrophilic inflammatory response but the MONONUCLEAR CELL INFILTRATE is more characteristic of most viral infections |
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Term
| Clinical tests for HSV1/2 |
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Definition
HSV antigen found in histologic sections by immunohistology
In latency: viral genome can be detected in approp ganglia by PCR or in situ hybridization |
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Term
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Definition
Primary stomatitis of HSV
in childhood -> latency
may be asymptomatic or a gingostomatitis and herpetic pharyngitis w/ oral vesicles, pain, fever
lesions last 5-12 days
HSV may become latent in sensory root ganglia of trigem nerve |
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Term
|
Definition
| HSV intraepithelial vesicles |
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Term
|
Definition
HSV
note Type A inclusions and multinuclearity |
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Term
|
Definition
HSV recurrent infection
activation is usually from single latent source so lesions are usually unilateral
hSV can be reactivated and excreted in saliva w/ no symptomatic lesions |
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Term
|
Definition
HSV keratoconjunctivitis
Dendritic ulcer of cornea that causes blindness |
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Term
|
Definition
herpetic Whitlow caused by HSV1/2
infects finger or nail area b/c of inoculation in skin
painful vesicular lesions of finger/pustules can be mistaken for bacterial infection
health care works at high risk! |
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Term
|
Definition
Brain biopsy of HSV encephalitis
usually in young adults - most common cause of sporadic enceph
Temporal lobe most common w/ focal neuro signs that resemble brain tumor/abscess
Brain biopsy shows perivascular lymphocytic cuffing
CSF doesn't have infectious virus but can detect viral DNA by PCR
HSV2 CNS infection more likely caues meningitis
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Term
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Definition
Generalized HSV infection in neonates. Transmitted through direct contact during vaginal birth w/ appearance on 2nd/5th day. Few cases are transplacental causing death
b/c of deficient T cell response |
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Term
|
Definition
Generalized HSV infection in adult
Opportunistic activation of latent infection in pts w/ AIDS/severe immunodef
eczema: develop disseminated eczema herpeticum
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Term
| Genitalis caused by which HSV strains? Why is detection important for pregnant women? |
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Definition
Both HSV2 and 1
need a C-section if HSV detected in at term woman or treat w/ acyclovir if before labor |
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Term
| Two syndromes caused by VZV |
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Definition
| Chicken pox (varicella) and shingles (zoster) |
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Term
|
Definition
| vesicular pattern of lesions and ability to establish latent infection in neurons w/ ability to reactivate to cause a localized vesicular eruption in a dermatome |
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Term
| Differences btwn VZV and HSV |
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Definition
| VZV is spread by respiratory route = very contagious; HSV via contact |
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Term
|
Definition
| spread by respiratory route = very contagious |
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Term
| Where and for how long does primary viremia of VZV occur? |
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Definition
| initiation of infection in respiratory mucosa or conjunctiva, primary viremia develops during 1-2 day prodromal period where virus replicates in regional lymphatics, liver, spleen |
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Term
| Where does VZV reside during latency? |
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Definition
dorsal root and/or cranial ganglia
Reactivation in old people and immunodeficient people causing shingles |
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Term
| Who is at risk for VZV reactivation? |
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Definition
| Reactivation in old people and immunodeficient people causing shingles |
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Term
| Describe secondary viremia in VZV |
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Definition
| from liver, spleen and lymphatics virus spread to the skin and dvlt of characteristic vesicular exanthema, fever and lesions |
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Term
| When is infectivity highest for chicken pox? |
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Definition
| 1-2 days prodromal before rash appears |
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Term
| Describe chicken pox presentation in children |
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Definition
| usually occurs before age 10 w/ incubation of 11-14 days. Vesicular/pustular eruption lasts 3-5 days w/ crusting that eventually resolves w/o scarring |
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Term
| Describe chicken pox presentation in adults |
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Definition
skin lesions may be atypical or absent and there may be severe necrotizing pneumonia as the primary infection
Primary infection can cause DIC in pregnant women and a fatal pneumonia in neonate |
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Term
| What areas of the body are most commonly affected in shingles? |
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Definition
| trunk, head and neck w/ opthalmic division of trigem nerve in 15% of cases |
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Term
| What does it mean if a child presents w/ shingles? |
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Definition
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Term
| What does shingles look like? |
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Definition
| Same vesicular rash like chicken pox but dermatomal, not disseminated |
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Term
| Common severe clinical symptoms of shingles |
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Definition
Post-shingles neuropathy w/ pain in the dermatome that may last for years.
Rarely if cervical/cranial (trigem ganglia) zoster, develop transverse myelitis or encephalitis |
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Term
| What does VZV lesion look like microscopically |
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Definition
| Similar to HSV w/ intraepithelial vesicles in multinuclear epithelial cells w/ Type A intranuclear inclusions and lymphocytic but often w/ a neutrophilic inflammatory infiltrate in a broken vesicle |
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Term
| What's the Tszanck test for? |
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Definition
Test for VZV
Scrapings from a vesicle applied to a microscope slide show intranuclear inclusions w/ multinuclearity
BUT IF IT'S NEGATIVE IT DOESN'T RULE OUT A HERPES VIRUS INFECTION |
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Term
|
Definition
| Chicken pox secondary viremia |
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Term
|
Definition
| VZV: microscopically similar to HSV w/ intraepithelial vesicles w/ multinuclear epithelial cells w/ type A intranuclear inclusions |
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Term
|
Definition
| Chicken pox infection in an adult |
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Term
|
Definition
|
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Term
|
Definition
| Latent phase of VZV infection |
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Term
|
Definition
| Shingles: reactivation of VZV infection |
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Term
|
Definition
| Shingles: reactivation of VZV - dermatomal pattern |
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Term
|
Definition
| Shingles: Type A intranuclear inclusions |
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Term
|
Definition
| body fluids-mucous membranes requiring direct contact |
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Term
| What is the primary infection of HCMV look like? |
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Definition
| most often asymptomatic and virus is excreted in urine, saliva, tears, semen, cervical mucous in some people for years VERY HIGH RATE OF ASYMPTOMATIC INFECTION |
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Term
| What is the site of entry for HCMV? |
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Definition
| epithelium of GU, upper alimentary or respiratory tract and virus can be found in sputum, mucus, blood urine and other secretions |
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Term
| Means of transmitting HCMV |
|
Definition
through sputum, mucus, blood, urine and other secretions
blood transfusion
organ transplantations |
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Term
| What impact does HCMV have on organ transplantation |
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Definition
| Adverse effect on transplant outcome esp when going from CMV+ to CMV- recipient b/c of the upregulation of major histocompatibility antigens |
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Term
|
Definition
| Persists in the host indefinitely as a latent infection in bone marrow and circulating leukocytes |
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Term
|
Definition
| Persists in the host indefinitely as a latent infection in bone marrow and circulating leukocytes |
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Term
| Describe reactivation in HCMV |
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Definition
frequent event triggered by immunosuppression.
Transplant: Pneumonitis, enterocolitis, viremia
AIDS: retinitis, pneumonitis, encephalitis, enterocolitis, fatal adrenal insufficiency |
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Term
| Can HCMV be controlled by humoral immunity? |
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Definition
NO. Ab against viral envelope glycoproteins may provide some protection (esp in congenital settings) but the virus is highly cell associated
CMI is essential for controlling infection |
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|
Term
| What is the most frequent opportunistic viral infection? |
|
Definition
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|
Term
| Microscopically what does HCMV look like? |
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Definition
Enlargement of cells (cytomegaly) w/ large single type A basophilic intranuclear inclusion and small cytoplasmic inclusions - cytomeg cells can be IDed in secretions
Sometimes binucleate (owl eyes) but not multinuc like HSV |
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Term
| What types of cells does HCMV infect? |
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Definition
| A wide spectrum: mononuclear leukocytes, macs, endothelial, epithelial, mesenchymal, neural and retinal, etc |
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Term
| What can cause EBV negative mononucleosis in older children and young adults? |
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Definition
HCMV 20-30% of the time
They may also have hepatitis! |
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Term
| What is clinical presentation of reactivation of HCMV? |
|
Definition
IMMUNOSUPPRESSED PATIENTS:
pneumonitis, enterocolitis and viremia in Aids: retinitis, pneumonitis, encephalitis, enterocolitis and generalized infections including adrenals that may cause fatal adrenal insufficiency |
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Term
| What is the most common congenital viral infection? |
|
Definition
HCMV but highly asymptomatic
Mostly occurs in 2nd/3rd trimesters; may subsequently develop motor and mental retardation |
|
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Term
| cytomegalic inclusion disease of newborn occurs with? |
|
Definition
symptomatic neonatal HCMV infection
hepatosplenomegaly, jaundice, thromocytopenia, cerebral calcifications, microcephaly, CMV nephritis, etc.
Usually occurs if mother had primary HCMV infection during pregnancy
Excrete cytomegalic inclusion bearing cells in urine that can be detected in urinary sediment |
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Term
| How can you prevent symptomatic HCMV infection of a neonate? |
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Definition
| Treat mother w/ primary infection w/ HCMV Ab |
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Term
|
Definition
| Cytomegaly w/ Type A basophilic intranuclear inclusion and small cytoplasmic inclusions seen in HCMV |
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Term
|
Definition
| Cytomegaly w/ Type A basophilic intranuclear inclusion and small cytoplasmic inclusion seen in HCMV |
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|
Term
|
Definition
Congential inclusion disease of newborn (CID)
w/ HCMV
hepatosplenomegaly, jaundice, thrombocytopenia, cerebral calcifications, microcephaly, CMV nephritis |
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|
Term
Describe the structure of herpesvirus family viruses
enveloped?
ds/ss DNA/RNA? |
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Definition
| Icosahedral capsid, enveloped, ds linear DNA, glycoprotein spikes, tegument proteins w/ lots of functions |
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Term
| Can HSV family be inactivated by detergents? |
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Definition
| YES b/c they're enveloped |
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Term
| How do HSV family viruses attach to cells? |
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Definition
Via glycoprotein spikes on virion and heparin sulfate molecules on cell
CAN BE BLOCKED W/ "NEUTRALIZING" Ab directed at glycoproteins |
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Term
| How do HSV family viruses penetrate into cells? |
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Definition
Usually Direct fusion at neutral pH
R Med Endo is less frequent |
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Term
| How does HSV family viruses get into the nucleus? |
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Definition
Virion loses envelope on entry = NO LONGER INFECTIOUS
proteins on nucleocapsid in cytoplasm mediate microtubule lead entry into the nucleus |
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Term
| What type of genome do the HSV family viruses have? |
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Definition
| ds linear DNA. In the nucleus the genome is circularized. |
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Term
| Functions of HSV family immediate early genes? |
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Definition
Modify the host
Upregulate other viral genes
Downregulate themselves |
|
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Term
| Function of HSV family Early genes? |
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Definition
Replicate the viral genome
Upregulate Late genes
Downregulate early genes |
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Term
| Function of HSV family late genes? |
|
Definition
Mainly structural - perform functions needed in earliest stages of infection: attachment, transport to nuclues, circularization, upregulate IE genes t/s
Downregulate early Genes |
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|
Term
What virus is associated w/ VP16?
What does it do? |
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Definition
HSV
Trans-acting factor that makes complex w/ host proteins and binds to IE promotors (ICP4 AND ICP0)
Late gene product that lives in the tegument and available upon entry of virus into new cell
Lost during travel down axon and so virus is latent in nucleus. spontaneously make Vp16 will turn on ICP4 and ICP0 |
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Term
| What virus is associated w/ ICP4? What is ICP4? |
|
Definition
HSV
ICP4 is an IE trans acting factor that turn on t/s of early and late genes and turns itself off.
At low levels it works with the VP16/host protein complex to recruit TFs and RNA Pol II.
At high levels it binds directly on the viral DNA and prevents production of itself |
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Term
| What virus is ICP0 associated with? What's its function? |
|
Definition
IE gene product of HSV
Modifies ubq-mediated proteolytic pathway causing destruction of certain host proteins that inhibit viral replication (modifies host)
Also disrupts IFN response to prevent cell from going anti-viral |
|
|
Term
| What are the early gene products of HSV family viruses? |
|
Definition
Thymidine kinase and DNA polymerase = promiscuous enzymes.
HSV DNA replicates by rolling circle mechanism |
|
|
Term
| Why does acyclovir prevent viral genome replication? What does PAA do? |
|
Definition
HSV thymidine kinase is promiscuous and so will add triphosphate to acyclovir and it gets incorporated into gene causing chain termination b/c no 3' to elongate
HOST DOES NOT DO THIS!
PAA is also recognized as a base triphosphate by viral DNA pol but not by host but this drug has bad SE. |
|
|
Term
| Where do the HSV family viruses get assembled? |
|
Definition
in nucleus on inner nuclear membrane - virions bud from inner nuclear membrane "primary envelopment".
This is lost when it fuses w/ outer nuclear membrane and is transported to the cytoplasm.
Tegument added near exocytic vesicles near the golgi. glycoproteins are gotten from membrane of these vesicles.
Nucleocapsid+tegument buds into the vesicles getting final envelope which is "secondary envelopment"
Exocytosed out of cell |
|
|
Term
| Does HSV get it's envelope from plasma membrane? |
|
Definition
NO. Most viruses do but HSV and coronavirues and PoX are exceptions.
HSV gets envelope from budding into vesicles. |
|
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Term
| What virus is associated w/ ICP47? What does it do? |
|
Definition
IE gene of HSV
Prevents expression of MHC molecules on cell surface by plugging up the TAP transporter which prevents transfer of degraded peptides into ER |
|
|
Term
| What virus is gC associated w/? What does it do? |
|
Definition
Late gene product of HSV
glycoprotein sits on virion and surface of infected cells and mimics the host C3b R and binds complement component of C3b and prevents activation of complement cascade |
|
|
Term
| What virus is associated w/ LAT? What does it do? |
|
Definition
HSV gene product
Only gene that is t/s during HSV latency.
Gene promotor for this has neuron specific elements, which is why HSV is latent in neurons.
anti-sense to ICP0 mRNA to block it's production
antiapoptic activity so neurons don't die |
|
|
Term
| What are the clinical symptoms of an adenovirus infection? |
|
Definition
acute febrile respiratory syndrome (not common cold)
epidemic conjuctivitis and infantile gastroenteritis |
|
|
Term
| What is the structure of adenoviruses? Envelope? ss/ds RNA/DNA? spikes? |
|
Definition
| Icosahedral capsid, naked, protein Fibrils (not spikes), w/ penton and hexon proteins in capsid. ds linear DNA genome |
|
|
Term
| How does adenovirus attach and penetrate into host cells? |
|
Definition
attach via fibers to specific cell R. Neutralizing Ab would prevent this.
R med endo (b/c noneveloped) |
|
|
Term
| How does adenovirus get to the nucleus? |
|
Definition
| uncoats in the endosome. needs acidification of endosome to get conformational change in capsid protein and DNA release into cytoplasm near nuclear pore. |
|
|
Term
| What are the goals of the early gene products of adenovirus? |
|
Definition
Both the goals of the IE and E of HSV.
induce cell into S phase of cell cycle
Protect cell from antiviral defenses
Produce viral gene products needed for viral DNA replication |
|
|
Term
| What virus has E1a? What does it do? |
|
Definition
adenovirus
transactivating early gene product.
Binds to Rb tumor suppressor and p300 and other TF to cause infected cells to enter S phase so cell makes nt that virus can use.
Also prevents the de novo production of protein kinase R (induced by IFN) which would break down the ds RNA made by adenoviruses |
|
|
Term
| What is virus has E1B? What does it do? |
|
Definition
adenovirus
transactivating early gene product.
Binds to p53 prevent the infected cells from undergoing apoptosis. |
|
|
Term
| What virus has 19kd E3? What does it do? |
|
Definition
Adenovirus early gene.
Binds to HLA (MHC)in the ER and prevents their transport to the cell surface |
|
|
Term
| What virus has 14.7 kd E3? What does it do? |
|
Definition
Prevents cell killing mediated by TNF by directly binding to it. Thus macs not recruted.
Also downreg Fas so prevents apoptosis.
Prevents release of AA (how TNF causes apop) so no pro-apo signal gets in |
|
|
Term
| What virus has 10.4kd E3? What does it do? |
|
Definition
adenovirus early protein
Binds to host's EGF R and is mitogenic.
Forcing other host into S phase to increase their Nt pool in prep for viral infection. |
|
|
Term
| What virus has VA RNAs? What do they do? |
|
Definition
Adenovirus
VA RNA's are short RNA fragments that prevent PKR from becoming a dimer
Two/more PKR molecules needed to bind to dsRNA to phosphorylate each other.
PKR then phos's eIF-2 that inhibits ribosome function.
PKR production is induced by IFN |
|
|
Term
| How does adenovirus get so many proteins from one promotor? |
|
Definition
| Late t/s comes from one major gene promotor. Different proteins come from mechanism of alternative splicing. |
|
|
Term
| What virus has TP? What does it do? |
|
Definition
Adenovirus.
Terminal protein acts as a primer for genome replication. It is covalently attached to a dCMP. It is attracted ed to repeats on the ends of genes, acts as a primer for daughter strand and prevents exonuclease activity |
|
|
Term
| How does adenovirus assemble and exit from a cell? |
|
Definition
capsomeres made in cytoplasm and transported to nucleus. Viral DNA attracted to capsid and are filled.
Exit via cell lysis. |
|
|
Term
| Effective drug/vaccine available for adenovirus? |
|
Definition
| Nope. Vaccine used for crowded places. |
|
|
Term
| Examples of paramyxoviridae? |
|
Definition
Paramyxoviruses
Parainfluenza viruses (upper and lower respiratory tract infections, including croup) Mumps viruses
Morbilliviruses
Measles (rubeola)
Pneumoviruses
Respiratory syncytial viruses (RSV)
Human Metapneumoviruses (HMPV) |
|
|
Term
| Which viruses have the surface proteins hemagluttin, neurominidase, G attachment, F protein? |
|
Definition
paramyxoviridae family
Paramyxo-HN
Morbilli-H
Pneumo-G
All have fusion protein to promote fusion of viral and host cell membranes and cause cells to become synciated = multinucleated giant cells |
|
|
Term
| Structure of paramyxoviridae family of viruses? ss/ds DNA/RNA? segmented? enveloped? |
|
Definition
Negative-sense, ss RNA viruses
Genome is NON-segmented. Enveloped
Surface proteins important in pathogenesis and immunity |
|
|
Term
| Similarities in all paramyxoviridae? |
|
Definition
similar morphologies
induce cell-cell fusion
initiate infection through resp tract |
|
|
Term
| Where does replication/ts occur for the paramyxoviridae? |
|
Definition
| CYTOPLASM b/c they're RNA virsues |
|
|
Term
| Method of transmission of measles? How contagious? |
|
Definition
| Respiratory aerosols from pt. VERY CONTAGIOUS even before symptoms present. No asyptomatic carriers. |
|
|
Term
| How many serotypes of measles? |
|
Definition
One
Immunity is after infection is life long. Vaccination works too |
|
|
Term
| Does measles cause viremia? How does it disseminate? |
|
Definition
YES. replicates locally in cells of respiratory tract, spreads to lymphoid tissue and then to RES where it infects WBC.
dissemination via viremia to other sites = symptoms appear
Orchitis
Aseptic meningitis
Sensory nerve hearing loss (transient)
Renal involvement
Pancreatitis and possible islet cell injury (?) |
|
|
Term
| How long is the incubation period w/ measles? |
|
Definition
|
|
Term
| Clinical symptoms of measles? |
|
Definition
cough, coryza, conjunctivitis, followed by high fever.
(complication: otitis media)
Koplik spots in mouth are pathognomonic for measles.
Rash on face that spreads. Improvement w/in 48hrs of appearance of rash. |
|
|
Term
| Which disease is associated w/ Koplik spots? |
|
Definition
MEASLES = PATHOGNOMONIC
grains of salt on red background - in mouth are pathognomonic for measles |
|
|
Term
| Describe measles rash and why you get it |
|
Definition
Rash on face that spreads. Improvement w/in 48hrs of appearance of rash.
maculopapular rash caused by immune CD8 T cells targeted to measles infected endothelial cells lining small blood vessels |
|
|
Term
| Why is there a greater risk for secondary infection w/ measles? |
|
Definition
Immunosuppression: Decreased DTH responses; decreased IL-12 responses, and increased risk for secondary infections
decrease in eosinophils and lymphocytes. Increase in levels of suppressive cytokines.
CMI important for clearance |
|
|
Term
| How do you prevent/treat measles? Vaccine? |
|
Definition
Live attenuated vaccine
MMRV (measles or rubeola, mumps, rubella, varicella)
First dose given between 12 - 15 months
Requires two doses
Treatment is supportive
Vitamin A in developing world
Isolation measures |
|
|
Term
| How do you diagnose measles? |
|
Definition
Clinical presentation: exposure, Koplick's spot and rash
Laboratory
Serodiagnosis: IgM antibody (when rash present) or IgG (need paired sera) |
|
|
Term
| How many serotypes of Parainfluenza virus? |
|
Definition
|
|
Term
| When and in whom do you most likely see parainfluenza virus infections? |
|
Definition
Fall/early winter.
Babies (croup), old people (pneumonia), adults (milder infections) |
|
|
Term
| How is parainfluenza virus spread? |
|
Definition
| Spread by direct contact or respiratory droplets |
|
|
Term
| What cell types to parainfluenza viruses infect? |
|
Definition
| infect epithelial cells in URT where they cause giant cell formation. |
|
|
Term
| Does parainfluenza cause viremia? How does it disseminate? |
|
Definition
|
|
Term
| Who gets croup? What is it caused by? |
|
Definition
Parainfluenza virus. Severe infection in infants causing bronchiolitis, pneumonia and croup (laryngotracheobronchitis)
Results in Low grade fever, runny nose, cough and stridor.
'seal-like or barky cough'
Children recover in 48hrs |
|
|
Term
| How do you develop immunity to parainfluenza virus? Vaccine? |
|
Definition
Infection produces short term protective immunity – both CMI and IgA.
Short lived
Reinfection is common but disease is milder
No vaccine |
|
|
Term
| How many serotypes of Mumps? |
|
Definition
|
|
Term
| What time of year is mumps most common? Who does it hit? |
|
Definition
| endemic in late winter and early spring, childhood infection if not vaccinated |
|
|
Term
| How is mumps transmitted? Contagious? |
|
Definition
Transmission via large-droplet aerosols, direct contact or fomites
Contagious before parotitis develops
b/c it's in the saliva before symptoms present or may have a subclinical presentation (1/3 of people) |
|
|
Term
| Viremia in mumps? How does it disseminated? |
|
Definition
| YES. Virus multiples in URT and in local lymph nodes. Virus enters blood and viremia can go to any organ. Generalized infection. Parotid gland swelling (hallmark of mumps), people have CNS/renal involvment |
|
|
Term
| How do you diagnose/prevent mumps? Vaccine? |
|
Definition
Prevention -Vaccine = MMR
Diagnosis of mumps: Many cases = subclinical, Parotitis is suggestive
Serum IgM Swab from parotid duct for viral isolation or PCR |
|
|
Term
| When does respiratory syncytial virus hit and who does it infect? |
|
Definition
|
|
Term
|
Definition
| Transmission is by close contact with contaminated fingers or fomites and by self-inoculation of conjunctiva or anterior nares. |
|
|
Term
| What is the most common LRT infection in kids under 1 caused by? |
|
Definition
|
|
Term
| Clinical manifestations of RSV? |
|
Definition
lower resp tract infection
bronchiolitis/pneumonia/otitis media in kids under 1
worse in old people/immunosuppresed
Older children/adults: URI "bad cold" w/ fever, rhintis, pharyngitis. bronchiolitis/pneumo may occur after URT infection |
|
|
Term
| Who at risk for lower respiratory tract disease with RSV |
|
Definition
Infants under 6 months
Infants and children with underlying lung disease
Premature infants
Immunocompromised patients
Patients with significant asthma
Elderly – especially institutionalized and with chronic pulmonary disease |
|
|
Term
| Viremia w/ RSV? How is it disseminated? |
|
Definition
NOPE. enters through nose/eyes and is confined to respiratory epithelium w/ progressive involvement of middle and lower airways. Moves cell-cell w/o extracellular phase
CMI role undefined. Reinfection w/ milder disease. |
|
|
Term
| What causes bronchiolitis? |
|
Definition
RSV
Feature: cough (for weeks), tachypnea, resp distress and in young infants hypoxemia, apnea, lethargy and poor feeding. |
|
|
Term
| How long do you shed virus w/ RSV? |
|
Definition
|
|
Term
| Diagnosis/vaccination/immunity for RSV? |
|
Definition
DX: Time of year (winter), age (<12 months), LRTI (especially bronchiolitis)
Respiratory tract secretions (virus isolation; antigen capture)
Maternal antibody does not protect infant from infection
Natural infection does not prevent reinfection
NO vaccine
Nosocomial infection: Handwashing!
High risk infants: passive immunization (prophylaxis) |
|
|
Term
| What are the clinical manifestations of HMPV |
|
Definition
Human Metapneumovirus
Disease spectrum like RSV but infects slightly older kids and causes more severe disease (hypoxemia, severe pneumo) in older kids |
|
|
Term
| What's the most common cause of infectious mononucleosis syndrome? |
|
Definition
|
|
Term
| What is the consequence of a primary EBV infection in early childhood? |
|
Definition
| Primary asymptomatic infection occuring early in childhood results in latency and persistence in subpopulation of B lymphocytes that might seroconvert |
|
|
Term
| What is the consequence of a primary EBV infection in older children or adults? |
|
Definition
| Overt symptoms are present - mostly IM. |
|
|
Term
|
Definition
| Oral secretions - saliva even in a person that is asymptomatic |
|
|
Term
| What population of cells does EBV infect? |
|
Definition
| Only human cells w/ CD21 R that is expressed on B lymphocytes and oropharyngeal/nasopharyngeal epithelium |
|
|
Term
| Describe primary infection of EBV. |
|
Definition
| Oral epithelium -> B lymphocytic lytic infection -> latency w/ episomal and/or genomic integration of B lymphocytes |
|
|
Term
| Why is it important that EBV has 3 types of latency? |
|
Definition
Type of Latency is dep on expression of different portions of viral genome.
EBV colonization of B cells can induce clonal expansion that interact w/ cytotoxic T lymphocytes.
Can lead to persistent lytic infection or continued B-cell prolif in immunosuppressed individuals like in post-transplant lymphoproliferative disorder (PTLD) and w/ clonal selection, malignant B cell lymphomas.
When they colonize other cells can cause epithelial and mesenchymal neoplasms (neopharynx, salivary gland, stomach) |
|
|
Term
| What causes the characteristic atypical lymphocytosis in EBV? |
|
Definition
infection of B lymphocytes in regional lymphatic tissue and blood cause activation of CD8+ T cells causes characteristic atypical lymphocytosis of acute IM.
Lymphoid hyperplasia w/ infiltration of parafollicular and medullary portions of cervical lymph nodes, can be mistaken for lymphoma.
Atypical lymphs in peripheral blood are mostly T cells that have been altered by cytokines (from CD4 that has interacted w/ infected B cells)
Could also be CMV mono, toxo, HIV in acute stage so serology necessary |
|
|
Term
| What is the clinical picture of EBV? |
|
Definition
in IM: pharyngitis w/ cervical adenopathy - may need steroids to prevent tonsils from closing larynx.
Splenomegaly w/ danger of rupturing spleen after you get better.
Liver: hepatitis - enlarged and tender
Also: encephalitis, myocarditis, renal disease, fatigue and fever |
|
|
Term
| How long is the course of EBV IM? |
|
Definition
| self-limiting at 2-4 weeks |
|
|
Term
| What is monospot (hterophile) agglutination for? |
|
Definition
Postive in 60-85% of EBV IM
IgM Ab for EBV capsid Ag (VCA) is positive in acute phase
IgG Ab to EBV are EB nuclear Ag means you're better
anti-EBNA shows prior EBV infection |
|
|
Term
| What virus is Burkitt's lymphoma associated w/? What is the mutation? |
|
Definition
EBV childhood cancer in equitorial Africa
activation of c-myc oncogene.
Malaria may be cofactor in B cell activation |
|
|
Term
| What virus is Nasopharyngeal carcinoma associated w/? How do you detect the virus's presence? |
|
Definition
Common in asians. Squamous carcinoma that develops years after EBV infection.
tumor cells have EBV DNA and Ag |
|
|
Term
| A transplant patient develops a B cell lymphoma. why? |
|
Definition
EBV
initially a polyclonal B cell expansion that may lead to monoclonal B cell lymphoma = POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) so don't use as much immunosuppressive drugs |
|
|
Term
| Why should you worry about EBV in an Aids patient? |
|
Definition
| B cell lymphomas w/ immunodeficiency (lymphoproliferative disorder) happens w/ severe immunodef and can cause primary lymphomas in solid organs like brain and liver w/o involving lymph nodes. |
|
|
Term
| What causes roseola infantum? |
|
Definition
HHV type 6
aka. exanthema suitum = febrile and transient rash syndrome |
|
|
Term
| Who gets roseola infantum? What cell population do they target? What are the symptoms? |
|
Definition
HHV6 infection of children under 2yo
Infects CD4+ T cells
High fevers, malaise, lymphadenopathy, febrile seizures. Rash occurs at the end and is associated w/ neutropenia.
rarely hepatosplenomegaly, enceph and mening |
|
|
Term
| What disease is caused by HHV-7? |
|
Definition
Roseola syndrome that affects children over the age of 2.
CD4+ lymphocytes targeted. |
|
|
Term
| What virus is associated w/ Kaprosi's sarcoma? Who normally gets this? |
|
Definition
HHV-8
AIDS patients develop vascular skin lesions |
|
|
Term
|
Definition
Kaposi's sarcoma in AIDS pts
Primary effusion lymphoma: body cavity-based B cell lymphoma
Plasmablastic form of multicentric Castlemena's disease in the mediastinum
Relapsing infalmmatory syndrome: joints, fever, splenomegaly, lymphadenopathy |
|
|
Term
| What is the genome of adenoviruses? How many serotypes? |
|
Definition
| ds DNA viruses w/ 51 different serotypes |
|
|
Term
| What cells do adenoviruses target? viremia? Latency? |
|
Definition
Epithelial cells. Viremia spreads them to visceral organs in immunocomp pts.
Remain latent in lymphoid tissue like tonsils, adenoids, peyer's patches and can be reactivated w/ immunosuppression. |
|
|
Term
| What are the clinical symptoms of adenovirus in children? |
|
Definition
URI, pharyngitis and conjunctivitis
PINK EYE common in winter
less common: hemorrhagic cystitis in girls, necrotizing pneumonia, pertussis-like illness, diarrhea |
|
|
Term
| How is adenovirus transmitted? |
|
Definition
|
|
Term
| What are clinical symptoms of adenovirus in adults? |
|
Definition
ARD w/ non-exudative pharyngitis cough, fever, cervical adenitis = military recruits rarely lead to necrotizing pneumonia.
conjunctivitis is also common |
|
|
Term
| What disease is associated w/ "smudge cells"? |
|
Definition
| Adenovirus - lung tissue w/ pneumonia, infected lung cells undergo necrosis and w/ intranuclear inclusions |
|
|
Term
| What does adenovirus infection look like histologically? |
|
Definition
Dense central basophilic intranuclear inclusion w/in infected epithelial cell. Can be tear shaped in eye scrapings.
NO cytomegaly. |
|
|
Term
| What are the classes of Papovaviruses? |
|
Definition
Polyoma viruses
BKV and JCV
Papillomavirus
warts, cervical dysplasia |
|
|
Term
| Who does the BK virus infect? symptoms? Latency? Reactivity? |
|
Definition
Primary respiratory infection in kids that can be asymp or mild resp infection.
Lives latently in renal tubulointerstitial cells.
Reactivates in IS pts (BAD for kidney transplants) |
|
|
Term
| Why should you worry about BK virus in kidney transplant patients? |
|
Definition
| Lives latently in kidney as integrated genome. Reactivtion in IS will cause renal nephritis. |
|
|
Term
| What disease is associated w/ the JC virus? |
|
Definition
| PML in AIDS pts. Remains latent in kidney and can reactivate to infect brain. |
|
|
Term
| What cells do HPV infect? |
|
Definition
Squamous epithelium of skin = warts
mucus membranes = chondylomas |
|
|
Term
| What types of the HPV virus cause chondyomas? |
|
Definition
types 16 and 18 = high risk
types 31.33.35 = interm risk
types 6,11 = low risk |
|
|
Term
| What virus is associated w/ E6 and E7? What do they do? |
|
Definition
HPV genes that are oncogenes
E6 binds p53
E7 binds p105
causes cellular prolif leading to malignant transformation |
|
|
Term
|
Definition
| Direct contact, sexual contact, fomites |
|
|
Term
| What causes verruca vulgaris? |
|
Definition
| Skin warts caused by HPV types 1-4 on hands/feet |
|
|
Term
| What causes laryngeal papillomatosis? |
|
Definition
| Common benign tumors of larynx caused by HPV6 and 11. Seen in infants b/c of vertical transmission. |
|
|
Term
| What causes condyloma acuminata? |
|
Definition
HPV 6 and 11 causes genital warts.
Resembles a stalk of broccoli on a mucous membrane. Microscope will show near-surface squam cells show small intranuclear inclusions and koilocytosis. |
|
|
Term
| What do HPV 16 and 18 cause? |
|
Definition
| Cervical dysplasia leading to cervical squamous carcinoma. Other squamous carcinoma like anogenital, head and heck have been associated w/ HPV. |
|
|
Term
| What virus is associated w/ koilocytotic atypia in squamous cells? |
|
Definition
| HPV will show this on a pap smear w/ cervical dysplasia, carcinoma. |
|
|
Term
| What mechanism does EBV use to cause lymphoma? |
|
Definition
| Upregs bcl2 gene preventing apoptosis to immortalize B cells. |
|
|
Term
| How does HTLV-1 cause cancer? |
|
Definition
| Tax gene t/s activates T cells -> t cell lymphoma common in Carribean or Japan |
|
|
Term
| How does HBV and HCV cause cancer? |
|
Definition
| DNA instability, accumulation of mutations - factor X caues clonal expansion causing liver cell cancer |
|
|
Term
| How does HHV-8 cause Kaprosi sarcoma? |
|
Definition
| viral oncogene by generation of p53 inhibitors and viral homologue of cyclinD preventing apoptosis in endothelial cells |
|
|
Term
| How is parvovirus B18 transmitted? What cells does it infect? How does it disseminate? |
|
Definition
| Respiratory route. Infects only metabolically active cells in S phase limited to erythroid precursors. Moves from URT to bone marrow. |
|
|
Term
| What is the biphasic disease process of Parvovirus B19? |
|
Definition
Lytic infectious phase where it can kill/inhibit growth of erythroid precursors
Second non-infectious immunologic phase |
|
|
Term
| What is erythema infectiosum? What virus causes it? |
|
Definition
'slapped cheek' rash in children/Fifth disease. Self-limited and no LT significance.
Occurs during noninfectious immunologic phase of parvovirus B19. and dissapears in 1-2 weeks |
|
|
Term
| Why is parvovirus B19 dangerous to those w/ sickle cell disease? |
|
Definition
| Can cause aplastic crisis causing profound reticulocytopenia and anemia. |
|
|
Term
| What can the immune complexes of parvovirus B19 cause in adults? |
|
Definition
| Rheumatoid arthritis. immunologic phase can be associated w/ severe arthralgia and frank arthritis. |
|
|
Term
| Why is parvovirus dangerous for people that are immunocomp? |
|
Definition
| Chronic symptomatic viremia and anemia |
|
|
Term
| Why is parvovirus dangerous for pregnang women? |
|
Definition
| Hydrops fetalis. Profound anemia and severe congestive heart fialure. |
|
|
Term
| What is the incubation period of variola? |
|
Definition
| Smallpox incubates 12 days w/ prodromal of 2-5 days of high fever, prostration, headache and backache followed by maculopapular and then vesicular rash that becomes pustular. |
|
|
Term
| What disease is caused by Variola? Describe clinical manifestation. |
|
Definition
SMALLPOX
2-5 days of high fever, prostration, headache and backache followed by maculopapular and then vesicular rash that becomes pustular. |
|
|
Term
| Describe rash of smallpox. |
|
Definition
maculopapular and then vesicular rash that becomes pustular.
STarts at mucosa of mouth, pharynx, face and forearms and goes to trunk. |
|
|
Term
| what disease is guarniere bodies associated w/? What are they? |
|
Definition
SMALLPOX - variola
scrapings of vesciles contain cells w/ intracytoplasmic inclusions displacing the nucleus |
|
|
Term
| Not that it's important anymore but why was vaccinating individuals that had immunodeficiency or ezcema or autoinoculation problematic in smallpox? |
|
Definition
| Vaccinia as a complication of small pox vaccination. Cutaneously spreading lesions but may become generalized w/ immunodeficiency. Vaccination may also lead to post-vaccinal encephalitis (demyelinating) that has an increased prevalnce in adults than kids |
|
|
Term
| What causes mulloscum contagiosum? What is it? |
|
Definition
Molluscum - pox virus causes benign skin tumors. Lesions are small pink wart-like tumors w/ central umbilication that occur on the face, arms, buttocks esp in AIDS pts. they last 1-2 years.
children > adults |
|
|
Term
| How is molluscum transmitted? |
|
Definition
| Direct contact and fomites. |
|
|
Term
| How would you diagnose Molluscum? |
|
Definition
CANNOT be culutured but can be PCRed
pathology is characteristic w/ epithelial cells having very large eosinophilic cytoplasmic inclusions compressing the nucleus to the periphery |
|
|
Term
|
Definition
Infectious mononucleosis-peripheral smear with atypical lymph |
|
|
Term
|
Definition
| Roseola Infantum - caused by HHV6 |
|
|
Term
|
Definition
| Kaposi sarcoma in AIDS caused by HHV8 |
|
|
Term
|
Definition
| Conjunctivitis - PINK EYE by adenovirus |
|
|
Term
|
Definition
Adenovirus conjunctivits-cytology-note intranuclear inclusion |
|
|
Term
|
Definition
| Adenovirus pneumonia-note necrosis and “smudge cells” |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
HPV
-cervical dysplasia-note mitotic figures and cytoplasmic vacuolation |
|
|
Term
|
Definition
PAP smear showing koilocytotic atypia
HPV |
|
|
Term
|
Definition
"slapped cheek" or erythema infectiosum
Parvovirus B19 |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Smallpox-large intracytoplasmic viral inclusions |
|
|
Term
| What type of genome does influenza A have? |
|
Definition
|
|
Term
| What cell types does Influenza A infect? Viremia? Dissemination? |
|
Definition
| infects resp epithelium in URT (in non-immune LRT). NO VIREMIA. |
|
|
Term
| What causes the extra-pulm symptoms of Influenza A? |
|
Definition
mac activation and cytokine release causing myositis, fever, etc.
Extra-pum sympt and lesions b/c of cytokines. |
|
|
Term
| What are severe complications of Influenza A? |
|
Definition
interstitial pneumo w/ diffuse alveolar damage (ARDS)
2ndary staph/strep pneumo associated w/ injury to cilia by virus b/c of loss of ciliary elevator
CHF - most common cause of death in elderly w/ flu
myoglobinuria (muscle necrosis) causing renal failure from tubular injury (myoglobin nephropathy)
Myocarditis, encephalitis |
|
|
Term
| Why is 2ndary infection common w/ Influenza A? |
|
Definition
| 2ndary staph/strep pneumo associated w/ injury to cilia by virus b/c of loss of ciliary elevator |
|
|
Term
| What cytokines cause alveolar cell necrosis and multi-organ system failure in Influenza A? |
|
Definition
| TNF-alpha and type 1 INF = cytokine stomr |
|
|
Term
| What is the genome of the parainfluenza viruses? |
|
Definition
|
|
Term
| What are the clinical manifestations of Parainfleunza in children? |
|
Definition
URT and LRT illnesses at all ages during late fall/winter seasons.
Young kids: laryngotracheobronchitis = croup. and bronciolitis obliterans w/ pneumonia |
|
|
Term
|
Definition
Bronchial and lung lesions show respiratory epithelial necrosis w/ mononuclear cell interstitial and peribronchial infilitrates w/ mucosal edema.
Rare syncytial giant cells in broncial and laryngeal mucosa.
NO INCLUSIONS |
|
|
Term
| If you see zones of atelectasis and other zones of compensatory hyperventilation in a chest X Ray, what virus do you think of? |
|
Definition
|
|
Term
| What disease is associated w/ Warthin Finkelday giant cells? What are they? |
|
Definition
MEASLES.
clusters of lymphocytes in lymphoid tissue |
|
|
Term
| What complication may occur in a child with measles that doesn't develop a rash? |
|
Definition
| Giant-cell pneumonia; have intranuclear and cytoplasmic inclusions. |
|
|
Term
| What is subacute sclerosing panencephalitis (SSPE) caused by? |
|
Definition
| MEASLES - defective virus that grows slowly in the brains of males - find intranuclear inclusions in brain b/c of defective virus that lives in glial cells. |
|
|
Term
| Clinical manifestations of mumps? |
|
Definition
Parotitis, orchitis, pancreatitis, encephalitis
In salivary gland: interstitial edema w/ infiltration by lymph, histiocytes, plasma cells.
Rare post-infectious demyelinating encephalitis. |
|
|
Term
| What viruses can cause meningioencephalitis? |
|
Definition
| direct viral invasion: HSV, ARBOVIRUS - WNV, ENTEROVIRUSES, HIV |
|
|
Term
| what can cause PostViral or post-vaccinal immune mediated encephalitis? |
|
Definition
vaccinations-vaccinia
post-measles, mumps etc.
T cell directed against components of myelin. Tends to involve only white matter and are called leukoencephalitis. |
|
|
Term
| What can cause slow virus encephalitis? |
|
Definition
| measles-SSPE, CJD, Kuru, -prion induced. |
|
|
Term
| What type of virus is WNV? Who is the def host, vector, accidental host? |
|
Definition
| RNA flavivirus that infects birds via mosquito vector. Humans are accidental hosts. |
|
|
Term
|
Definition
| YES. Viremic stage lasts 1-2 weeks. Can transmit via mosquito, blood transvusion, organ donation, breat feeding and transplacentally |
|
|
Term
| What percentage of people do you see symptoms in w/ WNV? |
|
Definition
| 1/5 but the rest seroconvert (IgM, IgG) have viremia for a week and be a donor. |
|
|
Term
|
Definition
self-limiting febrile flu-like illness w/ nausea, vomiting, diarrhea, muscle aches, and rarely rash
1/150 have headache, upper arm weakness, stiff neck, meningioencephalitis w/ confusion, flaccid paralysis-> coma and death |
|
|
Term
| Who is at high risk for WNV? |
|
Definition
| Old people. Immunosuppressed people. |
|
|
Term
| What is pathology of WNV? |
|
Definition
meningioencephalitis w/ gray matter of midbrain, brainstemand spinal cord ant horn cells like polio
Non-specific lymphocyte cuffing of vessels, neuronal degeneration, microglial nodules |
|
|
Term
| How would you diagnose WNV? |
|
Definition
| IgM serology, CSF has mononuclear cells (lymphocytes and monocytes), and protein gel serology on spinal fluid for WNV |
|
|
Term
| What are 3 strategies that RNA viruses use to get over the host cell's DNA bias? |
|
Definition
1. genomic RNA is one mRNA that makes a polyprotein that is cleaved into lots of other proteins
2. virion RNA is alternatively transcribed to yield lots of mRNAs using a RNA dep RNA pol
3. Have more than one piece of RNA as a genome
4. Retroviruses convert RNA into DNA |
|
|
Term
| Which RNA virsues encode a RNA dep RNA pol? |
|
Definition
|
|
Term
| How are rhinoviruses spread? |
|
Definition
|
|
Term
| How are picornoviruse colds spread? |
|
Definition
|
|
Term
| How are Polio and Hep A spread? |
|
Definition
|
|
Term
| How easily are picornoviruses desicated? |
|
Definition
| SMALL AND STABLE VIRUSES that live for looooong time on surfaces |
|
|
Term
| What is the structure of picornoviruses? genome? |
|
Definition
| dodecahedral naked capsid. Single stranded (+ strand) RNA. VERY SMALL w/ small genome. |
|
|
Term
| What is the Canyon Hypothesis and which virus does it relate to? |
|
Definition
PICORNOVIRUSES
the site where R attach on the virus is buried deep in canyons that are too small to allow the access of Ab |
|
|
Term
| What viruses employ ICAM as a R for attachment? Why is this important? |
|
Definition
Rhinovirus (picornovirus)
ICAMs are upregulated on cells in response to IFN which is a nonspecific host response to infection via the interferon response element (IRE).
Other gene t/s and t/l in the host is inhibited. |
|
|
Term
| How to picornoviruses penetrate into the cell? |
|
Definition
R med endocytosis
Need to acidify the endosome to cause conformational change in penton capsomere which can be blocked by neut Ab
OR
Virus gets close and squirts genome in cell |
|
|
Term
| Where to RNA viruses replicate? |
|
Definition
Entirely in the cytoplasm
EXCEPT INFLUENZA AND RETROVIRUSES |
|
|
Term
| What are the proteins associated w/ picornoviruses? |
|
Definition
| VP1, VP2, VP3, VP4, VP0 and 2ABC |
|
|
Term
| What virus is associated w/ VP0? What does it do? |
|
Definition
PICORNOVIRUS
After uncoating, VP0 molecules undergo autoproteolytic cleavage to destabilize the virioin, releasing the genome.
This also cleaves 2ABC to make 2A which is an active protease. |
|
|
Term
| What virus is associated w/ 2abc? What does it do? |
|
Definition
PICORNOVIRUS
Makes active protease 2A by cleavage by VP0.
Proteolytic enzyme specific for p220 which is a host phosphoprotein found in t/l initiation factor eIF-4F which is present in ribosomes.
By cutting p220 it destroys the Cap binding complex of the ribosome
W/o eIF-4F the ribosme subunits cannot assemble on capped mRNAs so host messages are not translatable |
|
|
Term
| Which virus' mRNA has a Internal Ribosome Entry site? Why is this important? |
|
Definition
Poliovirus! AKA the ribosome landing pad
mRNA has sepcial secondary structure that allows ribosomes to recognize and bind to viral mRNA so that it's the only functional message in the cell |
|
|
Term
| For what viruses does t/l come before t/s? |
|
Definition
RNA viruses! (picorno, polio)
T/l comes first b/c RNA dep RNA pol needs to be made |
|
|
Term
| What virus has the protein VPG? What does it do? |
|
Definition
PICORNAVIRUS
VPG is attached to 5' end of RNA to prime t/s rxn
VPG is cleaved from RNA by a host protease so that the RNA can serve as a message |
|
|
Term
| How does picornavirus regulate the timing of it's proteins? |
|
Definition
It makes one big polyprotein and then functional peptides are cleaved from precursor before t/l is even over.
Production is regulated by a series f timed proteolytic cleavages of the polyprotein |
|
|
Term
| Why does picornovirus need the host terminal uracil transferase protein? |
|
Definition
B/c it's a +RNA it needs to have the end of the mRNA poly-Ued at the end of the message.
This makes a hairpin and primes synth of - strand= this ds strand is a 'replicative form'
VPG and CMP attach to the end and primes the + strand synthesis- this is called the replicative intermediate. |
|
|
Term
| Why is picornovirus protein synthesis not interferec by PKR inactivation of eIF2? |
|
Definition
b/c it bypasses cap binding and elongation initiation steps!
That's why it can have dsRNA as a replicative intermediate! |
|
|
Term
| When does picornavirus RNA synthesis shift from t/s to genome replication? |
|
Definition
When there are so many VPG+strands that the host protease is overwhelmed. These strands then associate w/ procapsids in the cytoplasm.
VPG helps the strand get into the procapsid. |
|
|
Term
| How does the picornovirus shut into a stable conformation? |
|
Definition
VPO proteolysis step -> VP2 and VP4
and now ready for exit |
|
|
Term
| How does picornavirus exit the cell? |
|
Definition
|
|
Term
| What is the genome of influenza? Enveloped virus? |
|
Definition
| Single - stranded, segmented RNA genome. nucleocapsids are helical and virions are pleomorphic and enveloped! |
|
|
Term
| What virus is hemagglutinin associated w/? What does it do? |
|
Definition
Influenza! Attaches to sialic acid moities on host cell surface glycoproteins. acidification causes conformational change to show fusigenic site at the protease cleavage site that makes Ha1 adn Ha2 during viral maturation to allow envelope to fuse w/ endosome membrane and release nucleocapsid into cytoplasm.
Blocked by amantadine-HCL |
|
|
Term
| What virus is neuraminidase associated w/? |
|
Definition
Influenza! cleaves sialic acid off the cell glycoproteins. So virus can tunnel through mucous layer to the host's airway w/ repeated attaching and detaching.
Makes mucous watery so that droplets from a sneeze go farther. |
|
|
Term
| How does Influenza get into a cell? |
|
Definition
Direct fusion (influ B)
endocytosis (influ A) |
|
|
Term
| Where does influenza t/s occur? |
|
Definition
| IN THE NUCLEUS! 8 genome segments make 10 mRNAs by the virus's own RNA dep RNA pol |
|
|
Term
| How does influenza prime it's gene t/s? |
|
Definition
| RNA dep RNA pol steals cap and 15 bases from host mRNA and uses them to prime + strand synth |
|
|
Term
| What virus is associated w/ PB2, PA and PB1? |
|
Definition
Influenza!
PB2 is cap swipase
all of them are part of RNA dep RNA pol |
|
|
Term
| Why are influenza viruses preferentially t/l? |
|
Definition
B/c the virus steals the host's caps and their mRNA is degraded!
NS1 protein binds to polyA+ track of host spliced mRNA and stops them from leaving the nucleus |
|
|
Term
| What virus is associated w/ NS1? What does it do? |
|
Definition
NS1 protein binds to polyA+ track of host spliced mRNA and stops them from leaving the nucleus
NS1 itself is spliced and so it's mRNA doesn't leave. Thus this switches production of early genes (NS, NP) to structural late genes (M, HA, NA, Pol genes) |
|
|
Term
| What virus has NP? What does it do? |
|
Definition
| Influenza! it a structural peptide that is the signal for the switch from t/s to genome replication so full-length copy o the - genome is made |
|
|
Term
| Where does influenza assembly take place? |
|
Definition
| At the Plasma membrane - HA and NA are processed through the golgi and go the PM - matrix protein is bridge btwn cytoplasmic tails of glycoproteins and nucleocapsids |
|
|
Term
| Why are influenza virions specific for resp epithelium? |
|
Definition
| B/c the host cell protease on the surface cleaves HA into HA1 and 2 which is reuired for further fusion and infection |
|
|
Term
| What is antigenic drift? What virus? |
|
Definition
INFLUENZA!
Ab response is primarily to the HA and NA glycoproteins but these molecules mutate and so Ab are no longer protective. |
|
|
Term
| What is antigenic shift? Which virus? |
|
Definition
INFLUENZA!
b/c it has 8 segmented genes it can mix and match the genes that it transfers so you can get a whole new influenza virus that has never been seen - can get human, pig, bird mixes |
|
|
Term
| What is the most common cause of viral myocarditis in very young children? |
|
Definition
|
|
Term
| What is the most common cause of myocarditis/pericarditis in adults? |
|
Definition
|
|
Term
| What is the most common cause of aseptic meningitis w/ headache, fever and stiff neck? |
|
Definition
|
|
Term
| What are clinical manifestations of Echo virus? |
|
Definition
aseptic meningitis w/ meningismus
gastroenteritis
exanthems, conjucntivitis, enceph |
|
|
Term
| What are the congenitally transferred viral diseases? |
|
Definition
T remonema/toxoplasmosis
O ther (ParvoB19, Strep, list, chlam)
R ubella
C MV
H SV (VZV, HBV, HIV) |
|
|
Term
| What happens if a pregnant women is infected w/ rubella in the 1st trimester? |
|
Definition
100% of malformation
deafness, cataracts, congenital heart disease (patent ductus) |
|
|
Term
| What happens if a pregnant women is infected w/ rubella in the 2nd trimester? |
|
Definition
Lower than 100% chances of malformation
deafness, cataracts, patent ductus |
|
|
Term
| What happens if a pregnant women is infected w/ rubella in the 3rd trimester? |
|
Definition
|
|
Term
| What clinical signs does a pregnant women show of rubella infection? |
|
Definition
| Mild transient rash that might look like measles. Transient joint pain, swelling |
|
|
Term
| What is the time course of AIDS from the moment of infection? |
|
Definition
Acute phase disease = 3-6 wks after infection
Clinical latent period - still infective and may have renal, cardiac and CNS involvement - for years
Pre-AIDS: persistent generalized lymphadenopathy
AIDS 2ndary immune disease |
|
|
Term
| What does acute phase AIDs look like? |
|
Definition
Somewhat like IM but w/ macular rash
Diff b/c it's acute in onset, no tonsillary hypertrophy, no exudative haryngitis, no jaundice, can be diarrhea, opportunist infections occasionally |
|
|
Term
| Why is an ELISA an imperfect test for AIDS? |
|
Definition
Time course for dvl't of antibodies may be serologically - for wks/mo after infection
False positives - need to confirm w/ Western blot |
|
|
Term
| If a child was born whose mother had untreated HIV, what is the chance of transmission? What test would you perform on the infant? |
|
Definition
30-40% transmission
Have to use RT PCR, NOT AN ELISA- BABIES DON'T MAKE AB!! |
|
|
Term
| If someone w/ AIDs has CMV, what do they get? |
|
Definition
most common complicating virus infection!
retinitis, pneumonitis, GI involvement and generalized infectin w/ adrenalitis = adrenal insufficiency
Give acyclovir proph! |
|
|
Term
| If someone w/ AIDs had HSV, what would you see? |
|
Definition
| facial or anogenital infection lasting more than 1 month w/ generalized infection or localized involvement (esophogitis, pneumonia) |
|
|
Term
| If someone w/ AIDs had EBV, what would you see? |
|
Definition
| reactivation of latent infection causing hairy leukoplakia of tong and EBV associated B cell lymphomas in the brain |
|
|
Term
| If someone w/ AIds had the JCV, what would you see? |
|
Definition
| PML causes rapid CNS demyelination w/ atypical glial cells |
|
|
Term
| if someone w/ AIDS had HPV, what would you see? |
|
Definition
| generalized chondylomas, molluscum, etc. |
|
|
Term
| What is the most common opportunistic infection in AIDS? |
|
Definition
Pneumocytis carinii - pneumonia w/ high fatality w/o thearapy
MUST DO BAL for diagnosis and proph anti-PC Rx |
|
|
Term
| What would someone w/ AIDS get if they had candida infection? |
|
Definition
| oral thrush, esophogitis, other GI problems |
|
|
Term
| What if someone w/ AIDS gets a cryptococcus infection |
|
Definition
| most common cause of meningitis in AIDS - can occur in the pre-AIDS period |
|
|
Term
| What would happen if someone w/ AIDs gets a histoplasma infection? |
|
Definition
| may be reactivation of old pulm infection w/ generalized dissemination or severe fatal primary infection |
|
|
Term
| What are two parasites that AIDs pts can get? |
|
Definition
Toxoplasma - CNS involvment in gray matter
Cryptosporidium/microsporidium - watery chronic diarrhea w/ dehydration and malabsoprtion |
|
|
Term
| What would you see in a pt w/ AIDs and TB? |
|
Definition
| most likely reactivation w/ aggressive dissemination Pathology w/ necrosis but no granulomas |
|
|
Term
| What would you see in a pt w/ AIDS and mycobacterium avium intracellularae? |
|
Definition
| small bowel and massive involvement of lymph node w/ little/no granulomas but lots of acid-fast orgs in macs - late in AIDS w/ very low CD4 counts |
|
|
Term
| What are two neoplasms you see w/ AIDS? |
|
Definition
Kaposi sarcoma: HHV-8
B cell Lymphomas- EBV associated in organs like the brain |
|
|
Term
| What family does influenza virus belong to? |
|
Definition
|
|
Term
| What are the differences btwn influenza A, B and C? Which ones can do antigenic shift/drift? |
|
Definition
A is the most clinically important and causes seasonal/epidemic flu - infects multiple species
ONly one that can do antigenic shift and drift!
B: only infects humans - seasonal flu
Can only do antigenic drift!
C: rare but only infects humans |
|
|
Term
| What is the structure of influenza? |
|
Definition
| enveloped RNA virus w/ an internal nucleocapsid and envelope made up of an inner matrix protein, lipid bilayer and external glycoproteins |
|
|
Term
| What strains of influenza infect humans? What do you base strains on? |
|
Definition
| Based on HA and NA proteins - only H1-3 and N1-2 infect humans |
|
|
Term
| What sugars do influenza viruses bind to in humans? In birds? In pigs? |
|
Definition
| humans: alpha2-6 galactose Birds: alpha 2-3 galactose Pigs: Both |
|
|
Term
| What time of the year is flu season? |
|
Definition
| Dec- March; droplet spread w/ inhalation of airborne particles is the most common mode of transmission of flu infection |
|
|
Term
| What is the incubation period of influenza? Contagiousness period? When are flu titers the highest? |
|
Definition
Incubation period is 1-7 days where you're not contagious.
Contagious when you experience symptoms - highest fever = highest viral load in secretions |
|
|
Term
| What cells does influenza infect? |
|
Definition
Ciliated columnar epithelial cells.
Adhesion to epithelium mediated by interaction btwn the viral HA and cell surface R
Infection only in respiratory tract; no viremia
Nasal and tracheal ciliated cells undergo extensive necrosis early in course of illness. |
|
|
Term
| What causes the frequency of pneumonia w/ influenza infection? |
|
Definition
W/ alveolar involvement = true pneumonia
due to secondary staph or haemophilus infection |
|
|
Term
| What is the nature of protective response against influenza? Which Ab? |
|
Definition
Humoral
Predominant Ab is IgA in nasal secretions
IgG is predominant neutralizing Ab in tracheobronchial secretions.
Ig response is very effective - never are infected w/ same influenza virus
Some CD8 CTL responses against HA and NA important in clearance |
|
|
Term
| What are the clinical manifestations of influenza? |
|
Definition
Classic: abrupt onset of fever, flushed face, chills, headache, myalgia and malaise.
Most symp is b/c of IFN- mediated host immune response
Dry, hacking cough and coryza are common
Some leukopenia can occur |
|
|
Term
| How do you diagnose influenza? |
|
Definition
| Clinically. Virus can be readily gorwn esp if obtained w/ in first 72 hrs of illness |
|
|
Term
| What are the different types of influenza vaccines? |
|
Definition
Formalin-inactivated vaccines
Subvirion vaccines w/ lipid-containing membrane of virus disrupted or purified surface Ag-containing vaccines which are split-virus vaccines are save and very effective
Cold-adapted live, attenuated vaccines for intranasal use in healthy people that are not healthcare workers |
|
|
Term
| What virus can be prevented w/ Amantadine HCl? What other disease is this important for? |
|
Definition
Prevention of influenza infection: prevents intracellular uncoating of virual genome at endosomal level but no activity against Influenza B
PD: dopamine-enhancing agent |
|
|
Term
| Who is at the highest risk of H1N1 infection? How are symptoms different than seasonal influenza? |
|
Definition
Highest among 5-24yo followed by 1-4 yo. Elderly have previous immunity.
More GI symptoms than normal flu. |
|
|
Term
| What family does Rubella belong to? |
|
Definition
|
|
Term
| What is the genome of Rubella? Enveloped? Where does it replicate? |
|
Definition
| +SS RNA, enveloped that replicates in cytoplasm w/ humans as only reservoir |
|
|
Term
| What are the clinical manifestations of a nonpregant person w/ Rubella infection? |
|
Definition
Inoculation of virus into URT - prodromal phase of illness
Adenopathy is common w/ viral replication in regional lymph nodes
Viremia! Rash that is immune rxn. Arthritis b/c of immune complex deposition
Mild illness unless you're a fetus! |
|
|
Term
| What family does rhinovirus belong to? How many serotypes? |
|
Definition
PICORNAVIRUSES
100s of serotypes so you'll always get the cold! |
|
|
Term
| Describe the virion structure of rhinovirus. Enveloped? Genome? |
|
Definition
Capsid shell of 60 subunits w/ VP1-VP4 arranged in icosahedral symmetry.
Non-enveloped SS +RNA |
|
|
Term
| What is the structure/genome of coronaviruses? Where does it replicate? |
|
Definition
| spherical, enveloped, ss+RNA virus that replicates in the cytoplasm b/c it has a Met-cap and poly-A tail |
|
|
Term
| What cells does coronavirus infect? How do you tell the diff btwn a coronavirus and rhinovirus infection? |
|
Definition
URT infection
But it has potential of infecting LRT as well, including pneumonia and bronchiolitis
Infants: Gastroenteritis |
|
|
Term
| What cells does coronavirus infect? How do you tell the diff btwn a coronavirus and rhinovirus infection? |
|
Definition
URT infection
But it has potential of infecting LRT as well, including pneumonia and bronchiolitis
Infants: Gastroenteritis |
|
|
Term
| What family does SARS belong to? Symptoms? Why is it important? |
|
Definition
Coronavirus
high fever, chills, headache, discomfort, body aches. Mild resp symptoms and diarrhea
After 2-7 days have dry, nonproductive cough and then develop pneumonia w/ hypoxia
From Civet cat that has jumped to humans that is spread by close p-p contact, very contagious and transmitted by resp droplets w/ 11% mortality
Must quarantine 10 days post-fever b/c still contagious |
|
|
Term
| What family does enteroviruses belong to? What viruses are included in this genus? |
|
Definition
PICORNAVIRUSES
includes: polio, coxsackieviruses, echoviruses and other enteroviruses |
|
|
Term
| What is the structure of enteroviruses? genome? enveloped? Where does replication occur? |
|
Definition
small, naked icosahedral viruses w/ ss+RNA
replication and assembly occur in the cytoplasm
VERY RESISTANT TO acid pH (that's how it lives in the stomach) |
|
|
Term
| Who are the main reservoir for enteroviruses? Transmission? Seasonality? |
|
Definition
Humans!
Fecal-oral transmission
Occurs in late summer and early fall months |
|
|
Term
| Where do enteroviruses enter? Replicate? Is there viremia? |
|
Definition
Enter in the URT, oropharynx, intestinal tract
Replicates in lymphoid tissue/Peyer's patches
Viremia! Spreads throughout body.
Most are asympt infections or minor illness w/ fever and headache |
|
|
Term
| Do you develop immunity to enterovirus infection? CMI or humoral? |
|
Definition
immunity is serotype specific. Reinfection is asymptomatic.
Humoral immune response most imp |
|
|
Term
| How many people that contract polivirus develop symptoms? |
|
Definition
5-10%
Replication occurs in oropharynx and GI tract |
|
|
Term
| What is abortive polimyelitis? how often does it occur? |
|
Definition
nonspecific febrile illness: fever, vomiting, headache, malaise, sore throat of 2-3 days w/ no signs of CNS localization
4-5% |
|
|
Term
| What is aseptic meningitis (nonparalytic poliomyelitis)? How often does it occur? |
|
Definition
meningeal irritation: stiff neck, pain, stiffness in back
Recovery is rapid and complete
1-2% |
|
|
Term
| What is paralytic poliomyelitis and how often does it occur? |
|
Definition
viremic seeding of the brain and anterior horn cells of spinal cord leads to direct neuronal infection and neuronal death
.1-2% |
|
|
Term
| What is post-polio syndrome? |
|
Definition
| sequela of poliomyelitis that occurs 30yrs later in 20-80% of original victims. Poliovirus not present but syndrome is result from loss of neurons in initially affected nerves |
|
|
Term
| What are the polio vaccines? How effective? |
|
Definition
Inactivated polio vaccine
Oral polio vaccine (live, attenuated)
-shed in stool and can be transmitted to others to immunize them too
- if virus reverts causes vaccine associated paralytic poliomyelitis |
|
|
Term
| How is the clinical presentation of coxsackie/ECHO different from Polio? How many are symptomatic? |
|
Definition
Greater tendency to affect meninges and cerebrum and only a few affect anterior horn cells
60% are subclinical |
|
|
Term
| What is the most common clinical illness associated w/ Coxsackie/ECHO? |
|
Definition
Aseptic meningitis in children/young adults in the summer
Little clinicall that is diff from bacterial meningitis
Acute febrile illness w/ headache and meningismus
Can also cause myocarditis and pericarditis, febrile exanthematous syndromes, herpangina |
|
|
Term
| What causes hand-foot-mouth disease? |
|
Definition
Febrile Exanthematous syndrome
Enterovirus infection is leading cause of exanthems in children in summer and fall - looks like roseola.
Vesicular eruptions over extremities and oral cavities (yellow-white ulcers in mouth) |
|
|
Term
|
Definition
| Vesicular lesions in pharynx caused by Coxsackie A virus |
|
|
Term
| How do you diagnose an enterovirus infection? Therapy? |
|
Definition
Diagnosis is hard b/c symptoms are generic
Therapy is supportive
Lab diagnosis by isolation/ID of virus in cell culture, RNA detection |
|
|
Term
| What is the structure, genome of rotaviruses? Where does replication occur? |
|
Definition
icosahedral w/ double-layered capsid, ds, segmented RNA genome and RNA-dep RNA pol to transcribe individual RNA segments into mRNA
NO envelope = stable at RT and acid-stable
Replicates in cytoplasm |
|
|
Term
| Who does rotavirus infect? How is it transmitted? Seasonality? |
|
Definition
Young children 6mo-24mo
cooler monts
Spread fecal-oral |
|
|
Term
| What causes the diarrhea associated w/ rotavirus? |
|
Definition
Loss of brush border enzymes (sucrase, maltase, lactase)
Direct effect of rotavirus enterotoxin NSP4
Activation of enteric NS by infection |
|
|
Term
|
Definition
|
|
Term
| How do you develop immunity to rotavirus? Possible reinfection? |
|
Definition
Type-specific Ab that last for years
type specific IgA Ab in intestinal tract immunity to reinfection
Breastfeeding may be protective against rotavirus |
|
|
Term
| What are the clinical syndromes of Rotavirus? |
|
Definition
Acute gastroenteritis w/ incubation period of approx 48hrs: fever, vomiting for 1-3days, profuse diarrhea for 5-8days
Seldom blood in stool and fecal leukocyte tests are negative |
|
|
Term
| How do you diagnose Rotavirus? Treatment? |
|
Definition
clincial grounds: winter
Rotazyme test to confirm in stool. PCR
No specific treatment- fluid replacement
Vaccine is live |
|
|
Term
| What are the genera of calicivirus? |
|
Definition
| Norovirus and Sapovirus = cruise ship viruses!that are very contagious and cause epidemic gastroenteritis |
|
|
Term
| what is the structure of caliciviruses? genome? |
|
Definition
| small, naked, round, SS RNA that are hardy |
|
|
Term
| Who does caliciviruses infect? Seasonality? |
|
Definition
| year-round - most common in school-aged kids and adults but is 2nd to rotavirus in young kids GE |
|
|
Term
| How is calicivirus transmitted? |
|
Definition
Fecal oral but maybe aerosolized during vomiting
Mostly through food-service workers (CRUISE SHIPS) |
|
|
Term
| What is the immunity in calicivirus? Reinfection? |
|
Definition
| Humoral but no protection from reinfection |
|
|
Term
| What are the clinical manifestations of norovirus infection?viremia? |
|
Definition
Incubation of 1-2 days
Vomiting, diarrhea + generalized myalgias, malaise, headache, fever in 50% of cases
No blood/leukocytes in stool
Symptoms for 2-3 days and rapid recovery
No treatment |
|
|
Term
What are the fecal-borne hepatitis viruses?
What are the blood-borne hepatitis viruses? |
|
Definition
fecal: HAV, HEV
blood: HBV, HCV, HDV |
|
|
Term
| What is the structure of Hep A? Genome? What family does it belong to? Chronic disease? |
|
Definition
Non-enveloped capsid - stable virus
Positive-sense RNA genome (Picornaviridae)
NOT chronic |
|
|
Term
| How is Hep A transmitted? |
|
Definition
Transmission is fecal-oral
Close personal contact
Blood exposure (rare) (e.g., injection drug use, rarely by transfusion)
Spreads rapidly through a community because most people are infectious before symptoms appear |
|
|
Term
| What part of the world is Hep A found in? |
|
Definition
| Worldwide! Dev co, infection during childhood is asympt and mild |
|
|
Term
| Where does Hep A enter? Replicate? Viremia? |
|
Definition
Virus can withstand harsh conditions of the stomach and intestines after ingestion
Enters blood and travels to the liver where it causes transient viremia
Virus replicates in the cytoplasm of hepatocytes but does not produce cytopathic effects
Virus is released in high numbers into the bile, and excreted in the stool ~10 days before jaundice or detectable antibodies appears
Symptoms stem from immune-mediated damage to liver |
|
|
Term
| What causes symptoms of Hep A? Cancer? |
|
Definition
immune-mediated damage to liver
IFN limits replication but NK cells needed to lyse infected cells
Ab and complement also help viral clearance and cause pathology
IgM and IgG give immunity
NO CANCER |
|
|
Term
| Clinical manifestations of Hep A infection? |
|
Definition
abrupt onset of symptoms which can include fever, malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice
Adults more likely to have jaundice.
High levels of ALT and bilirubin.
99% complete recovery
.1% fulminant hepatitis, worse in old people |
|
|
Term
| What are lab tests for Hep A? Treatment? |
|
Definition
Time course of clinical symptoms, ELISA for IgM Ab during illness
No treatment
Prophylasis before exposure
2 vaccines for people >2: good for peole w/ chronic liver disease, clotting factor disorders |
|
|
Term
| What is the genome of Hep E virus? Family? |
|
Definition
| SS, non-enveloped RNA virus. Hepevirus |
|
|
Term
| Where is Hep E found? Transmission? |
|
Definition
Worldwide but mostly India, Asia, Africa and central america
Spread fecal-oral route, person-person is minimal |
|
|
Term
| What is the clinical presentation of Hep E? Chronic? Cancer? |
|
Definition
Causes only acute heptatitis
Same sympt as HAV: ab pain, anorexia, fever, hepatomegaly, jaundice, nausea, vomiting, high livere enzymes
HEV replicates in cytoplasm and is excreted in feces
No cancer! |
|
|
Term
|
Definition
|
|
Term
| How do you diagnose Hep E? Treatment? Vaccine? |
|
Definition
anti-HEV IgG, anti-HEV IgM not the best
Prevention to avoid contaminated water
No antiviral treatments, no vaccine in US |
|
|
Term
| What is the structure, genome of Hep B virus? Family? |
|
Definition
Enveloped, DNA virus of hepadnaviridae family
part ss, part ds, circular DNA molecule |
|
|
Term
| What are the important Hep B proteins? |
|
Definition
Hep B core antigen: capsid
Hep B e antigen: capsid part in blood
Hep B surface Ag: envelope part
Pol: RT and DNApol
X protein: causes cancer |
|
|
Term
| What causes the symptoms in Hep B infection? |
|
Definition
| not cytotoxic: symptoms b/c of immune response to viral infection |
|
|
Term
| How is Hep B transmitted? |
|
Definition
Through exchange of body fluids
Contaminated blood
Sex, IV drug use
Pernatal transmission in ASia, Southern Eruope, Africa, South America |
|
|
Term
| Describe acute infection after Hep B exposure? |
|
Definition
Less severe in children than adults (rarely kills overall)
Anorexia, nausea, weakness, fever, Rt-sided pain in ab
Hbs Ab cause viral clearance and provide protective immunity against reinfection
Resolves >90% of adults but only 10% of very young kids |
|
|
Term
| When can you first detect viral proteins after an Hep B infection? |
|
Definition
| Detectable viral proteins (HBsAg) take a month to appear in blood- window period where HBV infection hard to detect: IgM anti-HBcAg may be only detectable marker |
|
|
Term
| How common is acute liver failure or fulminant hepatitis w/ Hep B infection? |
|
Definition
May result in death
Occurs .1-1% of acutely infected people
More likely if co-infected w/ Hep D |
|
|
Term
| How common is chronic infection in Hep B infection? |
|
Definition
usually follows a mild/asymp initial infection
Constitutes a major reservoir of HBV worldwide
Genome will periodically integrate into host genome during replication
"Carrier state": normal ALT levels and nomral liver biopsy |
|
|
Term
| What antibodies/proteins are detectable in a person with carrier state Hep B infection? |
|
Definition
HbSag: pos
antiHbc: pos
anti-Hbs: neg |
|
|
Term
| What is the progression of chronic disease in Hep B infection? |
|
Definition
Progression of liver disease is variable (10-30yrs)
Cirrhosis and hepatocellular carcinoma are frequent in China |
|
|
Term
| What are the lab diagnosis for acute Hep B infection? |
|
Definition
Cholestatis
Serum ALT/AST levels
Serology: IgM anticore-Ag (Anti-HBcAg)
All people w/ HbsAg+ are potentially infectious
HBeAg positively coorelates w/ infectiousness |
|
|
Term
| What does the lab diagnosis of Chronic infection look like? |
|
Definition
Presence of HBsAg for more than 6 mo
Persistent elevation of serum ALT for more than 6 mo
Resolved, past infection is characterized by Anti-Hbs and IgG anti-HBc Ab |
|
|
Term
| What does serology of Hep B vaccination look like? |
|
Definition
|
|
Term
| How do you prevent/treat Hep B infection |
|
Definition
2 HBV vaccines
Hep B immunoglobulin from plasma of HbsAg+ persons, not used in US
Recombinant HBV DNA: plasmid w/ HBsAG
Treatment is supportive w/ IFN |
|
|
Term
If you are:
HBsAg+
Anti-HBc+
IgM anti-HBc-
Anti-HBs-
you are? |
|
Definition
|
|
Term
If you are:
HBsAg+
Anti-HBc+
IgM anti-HBc+
Anti-HBs-
you are? |
|
Definition
|
|
Term
If you are:
HBsAg-
Anti-HBc-
Anti-HBs+
you are? |
|
Definition
| Immune b/c of Hep B vaccination |
|
|
Term
| What family does hep C belong to? What is the structure and genome of Hep C? |
|
Definition
Flaviviridae family of virus
SS RNA genome that is envoloped and does NOT integrate into host genome
Structural proteins include core and 2 envelope glycoproteins
Non structural proteins: helicase, polymerase, several proteases
Viral proteins inhibit antiviral actions of IFN, inhibit apoptosis= prevent host cell death and promote viral infection |
|
|
Term
| How is Hep C transmitted? |
|
Definition
BLOOD - IV drug users, tranfusion, organ donors, hemophiliacs
High incidence of chronic, asymptomatic infection promotes spread of virus
Sex/perinatal are low risk |
|
|
Term
| How fatal is the acute infection of Hep C? how common is recovery? |
|
Definition
| Deaths are rare. 20% fully recover; 80% become chronic |
|
|
Term
| What is the time-frame of liver damage in Hep C? Cancer? |
|
Definition
20% develop cirrhosis over 20-30 years; 25% develop hepatocellular carcinoma
Most people are asymptomatic for years
Chronic infection more common w/ HCV than HBV |
|
|
Term
| How useful is the HepC virus antibody in detection of the disease? |
|
Definition
Not informative in early/acute infection - may take >4 wks to reach detectable levels
Clearing virus/therapy will remain HCV seropositive
Abnormal liver enzymes are first sign of infection. |
|
|
Term
| How informative is Hep C RNA in detection of disease? |
|
Definition
Qualitiative assay to measure +/- of HCV RNA is sensitive
Quantitative/viral load assay is less sensitive but allows monitoring of disease |
|
|
Term
| How do you treat/vaccinate for Hep C virus? |
|
Definition
Give recomb IFN alpha and ribavirin. 50% recover. BAD SE
No vaccine. |
|
|
Term
| What is the structure/genome of Hep D? Enveloped? |
|
Definition
Small circular -SS RNA
Nucleocapsid of HDV RNA+ delta antigen which is the ONLY protein
ENVELOPED W/ HBV ENVELOPE so there is always a coinfection
Replicates genome w/ RNA directed RNA Pol II |
|
|
Term
| How is Hep D transmitted? |
|
Definition
| Transmitted by blood, semen, vaginal secretions |
|
|
Term
| What is the clinical manifestations of Hep D? |
|
Definition
HDV/HBV coinfection and HDV superinfection during chronic HBV are associated w/ more severe liver disease than HBV alone.
Highest mortality of any Hep .
Fulminant hep is more likely to develop HDV than w/ other hep viruses
HDV causes liver damage directly b/c of CYTOTOXIC EFFECTS on hep +immune responses to both infections |
|
|
Term
| What is the lab diagnosis of Hep D virus? |
|
Definition
Serum anti-HD antibodies or delta antigen detected by ELISA
HDV RNA hybridization and RTPCR increase diagnostic precision |
|
|
Term
| What is the prevention/treatment of Hep D? |
|
Definition
Successful immunization against HBV protects against HDV infection
Treatment w/ extensive IFN therapy
HBV antivirals don't reduce HDV titers |
|
|
Term
| Describe the structure/genome of rabies virus. Family? Envelope? |
|
Definition
Bullet-shaped, enveloped, -sense SS RNA w/ 5 proteins
Rhabdovirus |
|
|
Term
| Where does replication occur w/ rabies virus? What is the histologic clue of rabies virus? |
|
Definition
| Replication occurs in the cytoplasm. Nucleocapsids accumulate in cytoplasm to form basophilic inclusions called Negri bodies! |
|
|
Term
| How is rabies transmitted? |
|
Definition
Zoonotic infection via the bite of an infected animal.
Urban rabies: dogs are primary transmitter
Sylvatic rabies: many species of wildlife are transmitter (raccoons, skunks, bats) - most common in US b/c of vaccination |
|
|
Term
|
Definition
| cases for which no evidence or history of animal bite is established |
|
|
Term
| How does rabies get into the CNS? |
|
Definition
Virus inoculated via saliva of animal
Viral replication in muscle for 1-2mo
Virion enters PNS
Passive ascent via sensory fibers
Replication in DRG
Rapid ascent in spinal cord
Infection of spinal cord, brainstem, cerebellum, other gray matter parts
Descending infection via NS to eye, salivary glands, skin and other organs |
|
|
Term
| Describe the prodrome phase of rabies. |
|
Definition
after weeks-months, virus enters the PNS and travels up the CNS to the brain
Symptoms: fever, headache, fatigue, paresthesia around site of bite |
|
|
Term
| Describe the neurologic phase of rabies. |
|
Definition
Infection of th brain causes classic symptoms
Seizures, disorientation, excessive sensitivity to light, touch, hydrophobia, progression to coma/death - agitated hallucinations followed by periods of lucidity |
|
|
Term
| How does the immune system fight rabies? |
|
Definition
| Doesn't elicit Ab response until late stage of disease - too late |
|
|
Term
| How is rabies diagnosis confirmed? |
|
Definition
usually post-mortem
Negri bodies: aggregates of viral nucleocapsids
Antigen detection: brain/skin biopsy, corneal epi cells - test of choice in live pt is detection of rabies Ag in nape of the neck
Serology: only after symptoms develop |
|
|
Term
| How is rabies prevented/treated? |
|
Definition
Ab can block progression of virus and the long incubation period allows active immunization as a post-exposure tratment
Local wound treatment
passive admin of human rabies immune globulin
vaccination: killed virus given post-exposure
Pre-exposure vaccination for vets
Prevent via animal control |
|
|
Term
| What are the 3 important arboviruse families? What are their characteristics? |
|
Definition
Togaviridae, Flaviviridae, Bunyaviridae
Transmitted by arthropod vectors
RNA genome
Toga/Flav = non-segmented, ss+RNA virus
Buny=segmented, ss-RNA virusees
Enveloped!
Replicate in cytoplasm |
|
|
Term
| Describe the urban and sylvatic cycles of Arboviruses |
|
Definition
Seasonal transmission w/ most infections in summer in temperate climates
Urban: large numbers of humans living living close to arthropods (mosquitos)
(urban dengue, urban yellow fever, St. Louis encephalitis)
Sylvatic: single nonhuman vertebrate reservoir may be involved - humans are accidentally infected (jungle yellow fever) |
|
|
Term
| How do arboviruses replicate in mosquitos? In humans? |
|
Definition
Female mosq get virus by taking blood meal from a viremic vertebrate host - virus multiplies in midgut epi cells, enters mosquito circulation, infects salivary glands where it replicates to high titers and is released into saliva
Human: virus enters circulation and gets into target cells (endothelial cells/RES)
Systemic symptoms: fever, chills, headache and other 'flu-like symp'
May produce enough virus for 2ndary viremia - major infection of target organs: brain access via infection of endo cells in blood vessels supplying brain |
|
|
Term
| How are arboviruses controlled by host immune system? |
|
Definition
CMI - good inducers of IFN that explains flu-like symptoms
Ab is important in controlling 2ndary viremia |
|
|
Term
| How do you diagnose, treat and prevent arbovirus infections? |
|
Definition
Diagnosis: clinical
Confirm by PCR at CDC
Treatment is supportive
Prevention is avoidance of arthropod
Live-attenuated vaccine against yellow fever virus |
|
|
Term
| What is the host, vector, 2ndary host for Eastern Equine encephalitis virus? What is the family? |
|
Definition
Togavirus
Marsh birds->Mosq->birds (humans accidental)
Atlantic and gulf coasts and Great Lakes
Rapid progression and high mortality (50-75%)- children at greater risk
Horses are sentinal animals |
|
|
Term
| What is the host, vector, 2ndary host for Western Equine encephalitis virus? What is the family? |
|
Definition
Togavirus
Bird->Mosq->Bird (humans/horses are accidental hosts)
Attack rate/illness is worse in children under 1
Horse are sentinal animals |
|
|
Term
| What is the host, vector, 2ndary host for St. Louis virus? What is the family? |
|
Definition
Flavivirus - major cause of arbovirus encephalitis in US
Bird->mosq->Birds (accidental in humans/horses)
No disease in horses so not sentinals
Major morbidity/mortality and highest attack rates are in adults over 40yo
Infants/young are spared |
|
|
Term
| What is the host, vector, 2ndary host for California/LaCrosse subtype virus? What is the family? |
|
Definition
Bunyavirus - common in OH
Chipmunks->mosq->chipmunks
Found in suburban/rural env'ts
Highest attack rates seen in individuals btwn 5-18yo.
Infection: abrupt onset of encephalitis, seizures |
|
|
Term
| What is the host, vector, 2ndary host for West Nile virus? What is the family? |
|
Definition
Flavivirus
Birds-Mosq-Birds Humans= accident, no p-p transmission
Most infections cause no symptoms. Small proportion get fever, headache, body aches, skin rash, swollen glands. Less than 1% get more severe illness like meningitis and encephalitis
Death: 1/1000 infections
Dead crows are sentinals |
|
|
Term
| What is the host, vector, 2ndary host for Yellow Fever virus? What is the family? |
|
Definition
Flavivirus
Monkeys -> Mosquitos in jungle -> Monkeys is the sylvatic cycle
urban cycle w/ humans as reservoir host
Abrupt onset of fever, chills, headaches and hemorrhage. May progress to vomiting, jaundice, and shock |
|
|
Term
| What is the host, vector, 2ndary host for Dengue virus? What is the family? |
|
Definition
Flavivirus
Most important mosq-borne viral disease
Human-mosq-Human
High Fever, headache, rash, back/bone pain
Severe form: dengue hemorrhagic fever/dengue shock syndrome |
|
|
Term
| What is the structure of Variola poxviruses? Enveloped? Genome? |
|
Definition
| Enveloped, dsDNA - largest and most complex of viruses. Replication in cytoplasm |
|
|
Term
|
Definition
| Human-human. Disease process begins by exposure through direct contact w/ bodily fluids/ aerosolized inhalation. |
|
|
Term
| How lethal is Variola major? Minor? What causes mortality? |
|
Definition
| 30% 1%. 2ndary bacterial infections are frequenlty cause of mortality |
|
|
Term
| Why was smallpox targeted for eradication? |
|
Definition
only infects humans and no reservoirs.
Vaccination known.
No sub-clinical presentation; can differentiate from other diseases; herd immunity, ring vaccinations |
|
|
Term
| What are common characteristics of the viruses that cause viral hemorrhagic fevers? |
|
Definition
All are enveloped RNA viruses
Dept on animal/insect natural reservoir (zoonotic)
Humans are not the natural reservoir- accidental hosts but they can transmit it to other humans.
Outbreaks sporadic and cannot be easily predicted
No vaccine/therapy |
|
|
Term
| What is the structure/genome of Dengue fever? Enveloped? What family does it belong to? Possible reinfection? |
|
Definition
| Positive strand, enveloped RNA flavivirus. 4 serotypes that don't provide cross-protection so can be reinfected. |
|
|
Term
| How is dengue transmitted? |
|
Definition
Human->Mosquito-> Human
Infects WBC and lymphatic tissues |
|
|
Term
| What are the clinical manifestations of someone getting dengue for the first time? |
|
Definition
Starts 4-7 days after bite
Fever, headache, generalized myalgias, nausea, vomiting; rash, minor hemorr
Many infections in kids are subclinical |
|
|
Term
| What causes dengue hemorrhagic fever/dengue shock syndrome? |
|
Definition
happens rarely w/ first exposure.
greater risk w/ 2nd infeciton w/ different serotype. Ab-dep enhancement of infection and increased autoimmunity
Rapid onset of capillary leakage, vascular permeability, thrombocytopenia, liver damage.
Fluids lost into tissue spaces can lead to shock; mortality rate 10-20% |
|
|
Term
| How do you diagnose dengue? |
|
Definition
Detection of viral proteins in blood during early infection/detection of IgM or IgGAb during late infection
PCR/virus isolation |
|
|
Term
| How do you prevent/treat dengue fever? |
|
Definition
Mosq control
Limited antivirals |
|
|
Term
| What is structure/genome of hantaviruses? Family? |
|
Definition
Enveloped, -RNA, segmented RNA genome.
bunyavirus |
|
|
Term
| How is Hantavirus transmitted? |
|
Definition
Rats asymptomatically carry virus and release in their feces, saliva, urine
No human-human spread |
|
|
Term
| Describe hantapulmonary syndrome. |
|
Definition
Incubation 1-5wks; rarely subclinical
Fever, myalgia develop days-wks after exposure, hypotension, progressive pulmonary edema, hypoxia
Late stage: hemorr, shock, kidney failure
Mortality of 35-50% from shock/hem |
|
|
Term
| What is the treatment/prevention/vaccine for Hantavirus? |
|
Definition
Vaccines for yellow fever/argentine hem fever.
Kill rats.
No great test for it. |
|
|
Term
| What are the structures/genomes of Marburg or Ebola? Family? |
|
Definition
| -ssRNA, enveloped glycoproteins to mediate virus entry. replication in cytoplasm. |
|
|
Term
| What is the means of transmission of Marburg/Ebola? Reservoir? |
|
Definition
Zoonotic viruses w/ unk animal reservoir (maybe bats)
Person-person involves close contact w/ infected body fluids: caring for dead bodies/funeral preps |
|
|
Term
| What is the mechanism of pathology caused by Marburg/Ebola? |
|
Definition
Envelope glycoprotein have cytopathic effects in human blood vessels
Downreg of cell adhesion and immune surveillance molecules
Pro-inflam cytokine activation from macs
Immune evasion by blocking neut Ab |
|
|
Term
| What is the clinical manifestations of Ebola/Marburg? |
|
Definition
Incubation of 3-9 days.
Severe headache, fever, chills, severe malaise, followed by nausea, vomiting, ab pain, diarrhea.
High fever on first day of illness, w/ progressive and rapid debilitating bleeding from everywhere
Death from severe blood loss
Mortality 50% for ebola/ 25% for marburg |
|
|
Term
| What is the treatment/prevention/vaccine for Ebola/Marburg? |
|
Definition
No treatment; supportive care.
Stay away from dead bodies! |
|
|
Term
| What is the structure/genome of HIV? Enveloped? |
|
Definition
| Two +RNA genomes that already has a cap and polyA attached. Some have icosahedral capsids, others w/ spherical/cone shaped core. Enveloped virions |
|
|
Term
| What are the functions of reverse transcriptase? |
|
Definition
Protease
RNA dep DNA Pol (RT)
DNA dep DNA Pol
Ribonuclease H
Integrase
specific t-RNA molecule required for priming reverse t/s |
|
|
Term
| How does HIV attach to a cell? |
|
Definition
| HIV attaches via gp120 to the CD4 molecule on CD4+T cells - macs are most imp |
|
|
Term
| How does HIV get inside the cell? |
|
Definition
By direct fusion.
Attachment exposes fusigenic region of gp41 which requires cofactors .
T cells:: CXCR4
Macs: CCR5
Fusion causes envelope to be lost. |
|
|
Term
| Where does HIV reverse transcription occur? |
|
Definition
Cytoplasm inside of the core structure so that RNA -> DNA before genome is released into cytoplasm.
If ATP and NTs are present (like semen), RT can occur in the absence of host cells: these virions are much more infectious than ones where RT doesn't occur - can't be inhibited by drugs |
|
|
Term
| Where does HIV get its primer from for reverse transcription? What is the product of this reaction? |
|
Definition
Primer comes from previous host cell. tRNA molecule that is antisense to priming site on +RNA
Product: dsDNA copy of genome where ends are duplicated (long terminal repeats= LTR) |
|
|
Term
| How does the HIV genome get into the nucleus? |
|
Definition
| the dsDNA copy of the genome w/ duplicated LTR at each end of the molecule. DNA then circularizes and enters nucleus w/ integrase still attached. |
|
|
Term
| What is the function of HIV integrase? |
|
Definition
| It is attached to the HIV genome as it enters the nucleus and it inserts the genome into a host chromosome randomly so that the host is infected for life. |
|
|
Term
| What are the 3 open reading frames of HIV? |
|
Definition
GAG: group specific Ag
POL: RTase (pol, RNAse, integrase, protease)
ENV: envelope glycoproteins |
|
|
Term
| What are the 3 possible cellular outcomes of HIV? |
|
Definition
latency: prevalent in T cells
Controlled replication: predominant in macs/dendritic cells
lytic replication: activated T cells |
|
|
Term
| What initiates t/s of HIV? |
|
Definition
| When a T cell is activated, NFkB binds to the LTR promotor region and Pol II will be recruited. |
|
|
Term
| What is the activity of the TAT protein in HIV infection? |
|
Definition
TAT is a trans acting factor that binds to TAR on the 5' end of the viral genome to allow POL II t/s to continue which increases viral t/s upto 1000X.
It also assists in transport to the cytoplasm and t/l functions. |
|
|
Term
| What is the function of the REV protein in HIV infection? |
|
Definition
binds to the cis sequence RRE in mRNA and prevents splicing of viral mRNA
This allows for gag, gagpol, env and genomic mRNA to be transported into the cytoplasm for t/l or genomic packaging. |
|
|
Term
| What is the function of NEF in HIV infection? |
|
Definition
1. Interacts w/ tyr and ser/tyr kinases to change the signaling pathways.
2. Increases the infectivity of the virus after the entry into the cell.
3. interaction w/ components of endocytic machinery decreases expression of CD4 and MHCI Ag on surface of infected cells. |
|
|
Term
| How does HIV switch form making gag to making gag-pol? |
|
Definition
| Termination codon for the GAG protein has a stem loop so that ribosome stalls and bounces back one NT which will make gag-pol |
|
|
Term
|
Definition
autocatalytic cleavage of core (GAG), core+enzyme (GAG+POL) polyproteins. These proteins would be myristilated and put in membrane for budding.
Protease inhibitors prevents this. |
|
|
Term
| How are oncogenic retroviruses made? |
|
Definition
They've picked up and modified normal cellular genes like GF or GFR. They're defective and need a helper virus to cause infection = acutely transforming retroviruses and cause lots of tumors in a short time.
Chronically transforming retroviruses insert in bad places so they cause clonal tumors that take decades to mature. |
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|
