Term
| How viruses exploit cells to make new viruses |
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Definition
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Term
| How virus replication causes disease and how viruses escape/interact with the immune system |
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Definition
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Term
| IMPORTANT: What are the characteristics of viruses |
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Definition
-Filterable agents (very small)
-Obligate intracellular parasites
-Minimal genetic info (efficient at overtaking host)
-Rely on host cell machinery to fulfill replication cycle
-Assembled from building blocks (don't divide like cells)
-Absolutely require host cell for replication |
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Term
| What is required for a virus to be successful? |
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Definition
Capable of transmission through potentially harsh environmental conditions
Traverse skin or other barriers of the host
Must adapt to the biochemical machinery of the host cell for replication
Escape elimination by the host immune response |
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Term
| What are the basic components of a virion? |
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Definition
DNA or RNA
Structural proteins (protects DNA/RNA)
Enzymes and nucleic acid-binding proteins (good targets)
Nucleocapsid (+ glycoprotein = envelope) or Naked capsid virus |
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Term
| How are viruses classified |
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Definition
Size
Morphology
Genome Type (DNA or RNA)
Means of Replication |
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Term
| What is the difference between a naked capsid virus and enveloped virus structurally? |
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Definition
naked capsid virus-has viral proteins assembled from subunits surrounding DNA or RNA (nucleocapsid) in an icosahedral shape
Enveloped virus has an addition lipid bilayer surrounding the nucleocapsid |
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Term
| What are the forms of viral RNA and DNA? |
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Definition
RNA
Single-strand
Double-strand
Linear
segmented
DNA
Double-strand
Single-strand
Linear
Circular |
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Term
| Can the naked capsids or the enveloped viruses withstand harsh environments? |
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Definition
Naked Capsids
Withstand harsh environmental conditions
Resistant to drying, acids, detergents
Many are transmitted fecal-oral route
Enveloped Viruses
Can't dry out
Not stable in acid
General must remain in body fluids (respiratory, blood) |
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Term
| What are two examples of enveloped viruses? |
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Definition
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Term
| IMPORTANT: What are the steps to virus replication |
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Definition
1. Recognition
2. Attachment
3. Penetration (engulfment)
4. Uncoating
5. Transcription (or Translation first)
6. Protein synthesis
7. Replication
8. Assembly
9. Lysis and release (naked capsid) or budding (enveloped) |
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Term
| How does the influenza virus and HIV recognize the cells? |
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Definition
Influeza virus-binds sialic acid
HIV- GP120 binds CD4 |
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Term
| IMPORTANT: How do naked viruses vs enveloped viruses enter the cell? |
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Definition
Naked Viruses: Typically endocytosis
Enveloped Viruses: Typically cell fusion |
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Term
| In general, where do DNA viruses and RNA viruses replicate? |
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Definition
DNA viruses- in the nucleus
RNA viruses- in the cytoplasm |
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Term
| Do DNA viruses use host cell machinery for transcription? What is the one exception? |
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Definition
-Generally use host cell’s DNA-dependent RNA Polymerase II to make mRNA’s when enter nucleus (some integrate into chromosomal DNA-very bad for us)
-Exception:Poxvirus family (Replicates only in the cytoplasm of cell so can’t use host cell’s RNA Polymerase II; instead, makes own enzymes) |
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Term
| Do RNA viruses use host cell machinery to transcribe and where do they transcibe? |
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Definition
| Must encode their own enzymes (host doesn't have RNA-dependent RNA polymerases) for transcription of mRNA and to replicate their full-length RNA genomes (plus and minus strands) in cytoplasm |
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Term
| IMPORTANT: What is the difference between plus and minus strand RNA viruses and what is the first step in each? |
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Definition
Plus strand RNA- genomes same sense as the mRNA (5'-3') 1st step is translation
Minus strand RNA- genomes opposite sense as mRNA (3'-5') 1st step is transcription to make plus stranded mRNA to translate |
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Term
| Which virus (DNA or RNA) polymerase is a good target for anti-virals? Why? |
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Definition
| RNA viruses because we don't make RNA-dependent RNA polymerases |
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Term
How do a retrovirus replicate?
What is an example of a retrovirus and what does the drug against it target? |
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Definition
Single-strand RNA to DNA by REVERSE TRANSCRIPTASE and then integrate into chromosomal DNA.
HIV- targets reverse transcriptase |
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Term
| How do viruses synthesize proteins? |
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Definition
| -All viruses depend on host cell translation machinery to make viral proteins from mRNA templates |
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Term
| Important: What is multiple proteins encoded from one mRNA by enzymatic cleavages of polyprotein catalyzed by viral encoded proteases? |
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Definition
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Term
| What is a way that drugs can target viral protein synthesis? (ex:HIV) |
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Definition
| Inhibit viral protease (can't cleave long polyprotein) |
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Term
| How do enveloped vs naked viruses exit the cell? |
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Definition
Enveloped Viruses: typically exit by budding from the cell
Naked viruses: typically exit through cell lysis (inefficient) |
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Term
| What is the interaction between the virus and the host |
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Definition
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Term
| What are the general steps to viral pathogenesis |
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Definition
1. Entry into the body (1. Fecal-Oral 2.Inhalation)
2. Primary Site of Replication
3. Viremia
4. Secondary Site of Replication in target tissues (more serious- ex: Ebola-infected macrophages migrate and cause more damage than virus itself) |
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Term
| IMPORTANT: What are the outcomes of virus infection at the cellular level? |
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Definition
1. Failed infection (abortive)
2.Cell death: Lytic viruses or Apoptosis (programmed cell death)
3. Infection without cell death
Chronic infection: no cell lysis, new viruses are produced (most likely enveloped)
Latent infection: limited production of viral components; no new viruses produced. Cellular properties may change later resulting in viral production (ex. Herpes Simplex Virus)
Transformation: Virus infection results in cell immortalization (conversion to a tumor cell)
Oncogenic viruses (HPV) |
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Term
| What are the host defenses against viruses? |
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Definition
Natural Barriers of the Body (ex. Skin)
Innate Immune Defenses (not antigen dependent- Interferon response, Macrophages, Dendritic cells, Natural Killer Cells)
Antigen-specific immune responses (vaccinations)
Antibodies, Helper T-cells
Cell-mediated immunity (Recognition of virus-infected cells, Lysis of infected cells) |
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Term
| What are the viral strategies to evade host defenses? |
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Definition
1. Preventing interferon action: Presence of double-stranded RNA in cell causes interferon overload
2. Changing viral antigens
3. Cell-to-cell spread: Evade antibodies (infected cell fuses with non-infected cell so no free viruses to kill)
4. Suppression of antigen presentation and lymphocyte function (hide from immune system) |
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Term
| What viral immunopathogenesis do respiratory viruses cause and what mediates it? |
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Definition
Flulike symptoms
Interferon, cytokines (virus is not actually causing flulike symptoms but the host is to prevent virus from replicating |
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Term
| Do plus-strand RNA viruses use the host cell's (transcription or translation machinery) to generate viral proteins? |
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Definition
| No involvement of the transcription machinery in the nucleus; so, the plus-strand RNA viruses produce their own enzymes for RNA transcription and replication, which recognize RNA as the template. The plus-strand RNA viruses do use the host cell’s translation machinery to generate viral proteins from a single gene (polyprotein) |
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Term
| Where do plus-strand RNA viruses replicate in the cell? |
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Definition
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Term
| What are the 2 classes of plus-strand RNA viruses with single-stranded, non-segmented plus-strand genomes? What makes them different from each other? |
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Definition
Class I and Class II
Class I-has 1 type of mRNA, long polyprotein that is cleaved
Class II- has multiple types of mRNA and one protein for each mRNA |
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Term
| Which is stable in the GI tract? Enteroviruses or Rhinoviruses |
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Definition
| Enteroviruses (Polio, Hep A, Coxsackie, Echoviruses) |
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Term
| How are Enteroviruses mainly transmitted? |
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Definition
|
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Term
| What is it called when enterovirus get into your blood stream? What happens? |
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Definition
Primary viremia
Targets tissue |
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Term
| What virus causes a mostly asymptomatic infection, with only a small faction of patients developing a paralytic disease by infecting motor neurons in anterior horn of spinal cord and the motor cortex |
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Definition
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Term
| In the poliovirus infection, how can you prevent progression to CNS (secondary tissue) to prevent paralysis? |
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Definition
| To make antibodies quick enough (basis for vaccines) before the virus reaches the secondary site to neutralize the virus |
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Term
_______ antibodies can prevent primary infection
_______ antibodies prevent viremic spread to target tissues |
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Definition
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Term
| IMPORTANT: What is the difference between the Salk vaccine and the Sabin Vaccine? |
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Definition
Salk Vaccine: Killed Virus (formalin inactivated), given as shot
Sabin Vaccine: Live, attenuated viruses, given orally. Attenuated strains can revert to virulent forms. Vaccinees shed the attenuated viruses in feces (Plusses, Minuses) |
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Term
What receptor does the Rhinovirus bind to in order to get inside the cell?
Where do antibodies bind on the Rhinovirus? |
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Definition
ICAM-1 receptor binds to Canyon on Rhinovirus surface
Antibodies bind on the ridge of the canyons |
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Term
| Why is it difficult to make a vaccine against Rhinovirus as compared to polio? |
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Definition
| Because Polio only has 3 serotypes while Rhinovirus has hundreds of different serotypes |
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Term
| What is the rhinovirus polyprotein's polymerase and protease? |
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Definition
polymerase- 3D^pol
protease- 3C^pro |
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Term
| What is the life cycle of plus-stranded RNA virus? |
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Definition
| plus stand --> proteins --> minus strand --> more plus strands |
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Term
Where and how do Rhinoviruses enter the host?
Where is it UNABLE to replicate? |
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Definition
Entry of virus into upper respiratory tract (Hands and fomites, Inhalation of droplets that contain virus)
Replicates at 33 degrees (temp of nose)
Unable to replicate in the GI tract (not stable to acid)--so we can swallow and kill it |
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Term
What class is the coronavirus?
Flavivirus (west nile)?
Picornavirus (Rhinovirus)? |
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Definition
|
|
Term
| What is the structure of the west nile virus? |
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Definition
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Term
What is the west nile virus replication cycle similar to?
What is west nile's receptor? |
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Definition
Picornavirus
alpha5beta3 integrin (in vertebrates-can spread to humans, birds, etc.) |
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Term
| What is coronavirus responsible for? |
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Definition
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Term
| IMPORTANT: What makes coronavirus so much different from rhinoviruses and west nile viruses? |
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Definition
| It has subgenomic mRNAs (one mRNA per protein)- like humans- while rhinoviruses and west nile only have 1 mRNA |
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|
Term
| What is the structure of the coronavirus? |
|
Definition
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|
Term
| What is the coronavirus receptor and where is it expressed? |
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Definition
ACE-2 (angiotensin-converting enzyme-2)
expressed in heart, lung, kidney, GI tract |
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Term
| Describe the structure for a minus RNA virus |
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Definition
| All helical (NOT icosahedral) and all enveloped (lipid membrane) |
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Term
Where do (-) sense ssRNA viruses replicate in the cell?
What virus is the exception? |
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Definition
Cytoplasm
Orthomyxovirus (multi-segment, influenza virus) |
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Term
| Are (-) sense ssRNA genomes infectious? |
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Definition
| NO- virion must contain proteins required for transcription bc host cell machinery doesn't recognize (-) sense genome |
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Term
Mononegavirales means?
What families are included in this order? |
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Definition
Mono- single segment of RNA; Nega- negative; Virales- virus
Bornaviridae
Filoviridae
Paramyxoviridae
Rhabdoviridae |
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Term
| What family is multi-segment, (-) sense ssRNA virus? |
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Definition
| Orthomyxoviridae (influenza virus)- 8 segments |
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Term
| What families is multi-segment, negative and ambisense ssRNA virus? |
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Definition
Arenoviridae (2 ambisense RNA segments)
Bunyaviridae (3 RNA segments) |
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Term
| What 3 types of viral proteins are essential? |
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Definition
Attachment/entry proteins
Structural/Assemble proteins
Replication proteins |
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Term
| What are the virus coding strategies |
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Definition
-Individual Open Reading Frames (multiple transcripts with transcription attenuation)
-Polyprotein processing (proteolytic processing)
-RNA editing (insertion/deletion)
-Multiple ribosomal initiation sites
-Stop codon read-through (don't recognize stop codon) |
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|
Term
| Why do viruses have coding strategies? |
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Definition
| viruses use the variety of mechanisms to maximize the amount of information that they get from relatively small genomes |
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Term
| What are the 3 viral replication proteins? |
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Definition
RNA-dependent RNA-polymerase (Transcription, Replication)
Nucelocapsidprotein (encapsidates RNA)
Phosphoprotein (accessory protein) |
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Term
| What does the RNA-dependent RNA polymerase do? |
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Definition
Transcription (Capping, methylation, polyadenylation) AND replication
Most conserved protein between the mononegavirales virus families |
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Term
| How does Transcription and Replication work for (-) sense RNA viruses? |
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Definition
Multiple polymerases bind and transcribe separate open reading frames (segmented) then translated by ribosome into proteins.
Then can replicate (continuous) RNA genome to make full length genome and then can assemble virions |
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Term
| What is the segmented genome virus that is ambisense that is mostly in rodent viruses that can be transmitted to humans (zoonotic)? |
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Definition
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Term
| What is the segmented genome virus that is ambisense that is mostly arthropod-borne viruses (some are rodent borne) |
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Definition
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Term
| What is a mononegavirales family that causes some of the exotic, hemorrhagic fever outbreaks (ex: ebola and marburg) |
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Definition
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|
Term
| What is the rhabdovirus that is caused by being bitten by an infected animal, going into the CNS, and secreted into the saliva? |
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Definition
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|
Term
| What is the paramyxovirus that is the major cause of lower respiratory tract infections in infants and no effective vaccine? |
|
Definition
| Human respiratory syncytial virus |
|
|
Term
| What is the paramyxovirus that is spread by respiratory secretions that causes a rash (not serious) but can cause systemic infections that can cause neurologic complications but there is an effective vaccine. |
|
Definition
|
|
Term
| What are the types of influenza virus and which ones are most serious/has vaccines? |
|
Definition
A-most serious, involves upper and lower respiratory tract, has vaccine
B-similar to A but more mild, has vaccine
C-not serious, upper respiratory illness, no vaccine |
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Term
| What are the 2 glycoproteins on the lipid bilayer of the influenza virus? What do they do? |
|
Definition
Hemagglutinin- attachment to host cell
Neuraminidase- cleaves sialic acid after virion enters the host cell
Good targets for vaccines |
|
|
Term
| What protein is not found in other viruses except influenza and is involved in virion uncoating, required for the full replicaiton cycle, and is a target for Amantadine? |
|
Definition
|
|
Term
| What are the 3 major types of influenza virus variation techniques? |
|
Definition
Antigenic drift (single AA change)
Antigenic shift (major change)
Recombination (rare) |
|
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Term
| Why are pigs (as opposed to birds) so important in transmitting the pandemic influenza virus to humans? |
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Definition
| Pigs can be infected by both human and avian (bird)-like influenza virus by attaching to receptors on their tracheal epithelial cells. Pigs acts as a "mixing bowl" for making new variant. |
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|
Term
| How can we keep from being infected by influenza? |
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Definition
Antiviral drugs (Neuraminidase inhibitors, Ion channel blockers)
Vaccines |
|
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Term
| What are the 3 groups of DNA viruses that infect humans? |
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Definition
Group I-dsDNA virus families (largest group)
Group II-ssDNA families
Group III- DNA genome that replicate through an RNA intermediate |
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Term
| Are RNA or DNA viruses larger? |
|
Definition
|
|
Term
Is DNA or RNA viruses:
more stable
more error-prone replication
Protected by cell
packaged into preformed capsid shells |
|
Definition
DNA is very stable (RNA less stable)
RNA is more error-prone replication, small genomes (DNA is accurate replication, large genomes)
DNA is protected by cell (dsRNA actively degraded by cell)
DNA is packaged into preformed capsid shells-procapsids (RNA co-assembles with capsid protein) |
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Term
| Is DNA replication unidirectional or bidirectional? |
|
Definition
|
|
Term
| How do DNA viruses make sure that their ends are replicated correctly? |
|
Definition
| they have circular genomes or use special terminal proteins |
|
|
Term
| Where do DNA viruses replicate and where are the proteins synthesized |
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Definition
Nucleus
Proteins are synthesized in the cytoplasm and imported into the nucleus |
|
|
Term
| What are some advantages to DNA virus replication as opposed to RNA? |
|
Definition
DNA is protected by the cell
DNA viruses can use replication (DNA>DNA) and transcription (DNA>RNA) machinery of host (while RNA viruses have to encode their own polymerase) |
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|
Term
| What are some ways thats DNA viruses get their DNA into the host nucleus? |
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Definition
1. Enter through nuclear pore (size limit)
2. Disassemble in cytoplasm and transport genome/protein complex
3. Eject DNA at nuclear envelope (like bacteriophage) |
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|
Term
| How do DNA viruses get around the major challenge of requiring infection of ACTIVELY GROWING CELLS |
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Definition
Infect actively growing cells (parvo)
Activate the cells (polyoma)
Viral latency (herpes)
Co-infect with helper virus (adeno) |
|
|
Term
| What are most antiviral drugs and how do they work? |
|
Definition
nucleoside analogues
analogs of normal nucleoside are incorporated into the chain and leads to chain termination bc analog lacks 3' end so can't elongate any further |
|
|
Term
| What causes "fifth disease" (rash, fever) in children and arthritis in adults? |
|
Definition
| B19 erythrovirus-parvovirus |
|
|
Term
| In the "fifth disease", is the rash caused by the virus or the immune response? |
|
Definition
|
|
Term
| What type of cell do parvoviruses infect, how does it enter the nucleus, and how does it exit the nucleus? |
|
Definition
• Parvoviruses need to infect actively growing erythroid precursor cells (bone marrow)
• Enter nucleus intact (small size)
• Exit nucleus/cells by lysis |
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|
Term
| Does the parvovirus require a primer to replicate? |
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Definition
| No-- end of genome form terminal self-priming hairpins that loops so no shortening |
|
|
Term
| What are the 2 Papovaviruses and what disease do they cause? |
|
Definition
Polyomavirus- doesn't normally cause disease in humans unless immunocompromised
Papillomavirus- causes warts, cervical cancer |
|
|
Term
| How do Polyomavirus replicate and what is required to recruit the host DNA pol to the origin? |
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Definition
"theta" replication (circular, bidirectional)
"Large T antigen" recruits DNA pol to origin |
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|
Term
| What stimulates entry into S phase (host cell specific) in permissive cells and integration of the viral genome may lead to transformation in non-permissive cells? |
|
Definition
|
|
Term
| What layer of the skin do papillomaviruses cause warts and how do they cause cervical carcinoma? |
|
Definition
granular layer
• HPV may cauce cervical carcinoma by integrating into the host genome, expression of E6 and E7 oncogenes
– inactivate tumor suppressor genes |
|
|
Term
Do Adenoviruses use_________ to prime DNA replication instead of DNA/RNA primers
Is there a lagging strand? |
|
Definition
|
|
Term
| What is a DNA virus that is very common, causes high fever, sore throat, conjunctivitis (shipyard eye), very resistant (non-enveloped), spread from person-person, and no vaccine available. |
|
Definition
|
|
Term
| Describe the herpesvirus structure |
|
Definition
icosahedral nucleocapsid core
amorphous tegument layer
envelope with glycoproteins |
|
|
Term
| How do herpesvirus get their DNA into the host nucleus? |
|
Definition
| inject the DNA into the nucleus |
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|
Term
Assembly and DNA packaging in herpesviruses resemble tailed dsDNA ________.
DNA replication via ________ mechanism that forms DNA ________.
Formation of _____ precursors, using a scaffolding protein.
DNA is packaged into procapsid through a _______.
Concatemeric DNA substrate is packaged by a ______ complex |
|
Definition
bacterophages
DNA replication via rolling-circle mechanism forms DNA concatemers
Formation of procapsid precursor, using a scaffolding protein
DNA is packaged into procapsid through a portal
Concatemeric DNA substrate is packaged by a terminase complex |
|
|
Term
What is a hallmark of herpesvirus infections?
Is there a treatment for this? |
|
Definition
latency
No treatment for latent virus (only treatment for active virus) |
|
|
Term
Where does the poxviridae (smallpox, vaccinia [cowpox]) replicate?
Do they use the host cell machinery or their own? |
|
Definition
Cytoplasm in "viral factories"
These viruses need to synthesize all the enzymes required for DNA replication and transcription |
|
|
Term
| Plus strand RNA viruses use the host's transcription or translation machinery or both? |
|
Definition
| translation machinery ONLY (bc replication occurs in cytoplasm) |
|
|
Term
| Antiherpesvirus drugs are nucleoside analogues that ________ |
|
Definition
| Antiherpesvirus drugs are nucleoside analogues that block replication |
|
|
Term
| Is there a treatment for the latent herpesvirus? |
|
Definition
| No treatment for latent virus (only treatment for active virus) |
|
|
Term
| The viral herpes genome exists as an ______ (naked, circular DNA) in the host cell nucleus |
|
Definition
|
|
Term
What are the different strategies viruses use for compactness/efficiency:
|
|
Definition
1.Separate mRNA’s for each viral protein
2.Polyprotein strategy |
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