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Virology
DNA viruses
87
Microbiology
Undergraduate 2
05/10/2011

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Term
DNA Viruses
Definition
Adenovirus.
Hepatitis B.
Herpes Simplex I.
Herpes Simplex II.
Cytomegalovirus.
Epstein Barr Virus.
Varicella Zoster.
Human Papilloma Virus.
Human Parvovirus B19.
Variola.
Vaccinia.
Term
Adenoviridae
Definition
Adenovirus (DNA)
Term
Hepadnaviridae
Definition
Hepatitis B (DNA)
Term
Herpesviridae
Definition
Herpes Simplex I.
Herpes Simplex II.
Cytomegalovirus.
Epstein Barr Virus.
Varicella Zoster.
(DNA viruses)
Term
Papillomaviridae.
Definition
Human Papilloma Virus (DNA)
Term
Parvoviridae
Definition
Human Parvovirus B19 (DNA)
Term
Poxviridae
Definition
Variola.
Vaccinia.
(DNA)
Term
Specimens for Adenovirus diagnosis
Definition
Stool.
Urine.
Throat.
Conjunctiva.
Rectal swab.
Virus excretion may last from days to weeks.
Term
Treatment for Adenovirus
Definition
No treatment.
Term
Incubation period for Adenovirus
Definition
About one week.
Term
Transmission of Adenovirus
Definition
Direct contact, fecal-oral route, respiratory droplets or fomites (inanimate objects capable of transmitting pathogens)
Term
Properties of Adenovirus
Definition
Icosahedral. Double stranded DNA. No envelope. Has protein "fibers". Replicates in nucleus. Narrow host range. ~50 serotypes (<1/3 responsible for most disease)
Term
Infectious cycle of Adenovirus
Definition
~24 hours.
Term
Replicative cycle of Adenovirus
Definition
Attachment, penetration, uncoating.
Uncoating completed in the nucleus.
Virus assembly occurs in the nucleus.
100,000 virus particles per cell.
Term
Pathogenesis of Adenovirus
Definition
Infects epithelial cells only.
Usually does not spread beyond regional lymph nodes.
May persist as latent virus in adenoids and tonsils.
Cytopathic effect: cell enlargement, rounding.
Term
Insidious onset.
Elevated liver enzymes. Jaundice.
Serum sickness-like syndrome:
fever, rash, polyarteritis nodosa.
Outcomes vary; HBsAg positivity.
Definition
Symptoms of Hep. B (HBV)
Term
Pathogenesis of Hep B
Definition
Infected hepatocytes. Localized areas of liver necrosis. Damage is reversible with recovery. Chronic hepatitis with HDV co-infection. Hepatocellular carcinoma occurs in ~1% of cases.
Term
Replicative cycle of Hep. B
Definition
Similar to Adenovirus. Final assembly occurs outside of nucleus.
Term
Properties of Hep. B
Definition
Icosahedral. DNA, double stranded.
Enveloped. Major proteins HBsAg and HBcAg.
Replicates in nucleus through RNA intermediate.
Many different types with different host range.
Term
Diagnosis of Hep. B
Definition
Serology.
Antigen - HBsAg.
Antibody - Anti-HBcAg (IgM), Anti-HBsAg, Anti-HBcAg (IgG)
Term
Treatment for Hep. B
Definition
Interferon. Antivirals directed at viral replication. Surgery (transplantation).
Term
Incubation period for Hep. B
Definition
2-3 months.
Term
Transmission of Hep. B
Definition
Blood borne. STI.
Transfusion associated.
Term
Adenovirus and Hep. B are both found where?
Definition
Worldwide.
Term
Vaccine for Hep. B?
Definition
Yes.
Term
Structure of Herpesviridae viruses
Definition
Large icosahedral viruses (150-200 nm)
Double stranded DNA genome.
Enveloped (Derived from nuclear membrane)
Encodes for >100 viral specific proteins.
Term
Biological properties of Herpesviridae viruses
Definition
Growth cycle may be short to long.
Cytopathology may be cytolytic or cytomegalic.
Cell tropism related to latency may involve: Neuronal cells, lymphoid tissue, specific organ cells (kidney, etc.)
Antigenic variability.
Term
Virus replication of Herpesviridae viruses
Definition
Virus envelope fuses with host cell.
Nucleocapsid transported into nucleus.
Uncoating occurs.
Viral DNA is transcribed, replicated.
Large number of viral specific proteins generated, some are enzymes.
Replicative cycle ranges from 18 hours (HSV) to >70 hours (CMV)
Term
Disease caused by Herpesvirus 1
Definition
HSV I (Herpes Simplex I)
Term
Disease caused by Herpesvirus 2
Definition
HSV II (Herpes Simplex II)
Term
Disease caused by Herpesvirus 3
Definition
Varicella-zoster virus
Term
Disease caused by Herpesvirus 4
Definition
Epstein-Barr virus (EBV)
Term
Disease caused by Herpesvirus 5
Definition
Cytomegalovirus (CMV)
Term
Disease caused by Herpesvirus 6
Definition
HHV 6 (Human Herpesvirus 6)
Term
Disease caused by Herpesvirus 7
Definition
HHV 7 (Human Herpesvirus 7)
Term
Disease caused by Herpesvirus 8
Definition
Kaposi's Sarcoma HHV
Term
Symptoms of HSV I
Definition
Oropharyngeal - Often asymptomatic;
Fever, pharyngitis, vesicular lesions,
gingivostomatitis, lymphadenopathy
(recurrent disease may present as painful "fever blisters")

Keratoconjunctivitis - Corneal ulcers,
vesicular lesions on eyelids; significant
cause of corneal blindness.
Term
Symptoms of HSV II
Definition
Genital - Vesicular ulcerative lesions
of penis, cervix, vuvla, vagina; may be
associated with fever, dysuria, lympadenopathy;
recurrances are common and often asymptomatic in women.

Encephalitis - Fever, headache, vomiting,
seizures, paralysis; high fatality rate.

Neonatal - usually in three forms:
Cutaneous, encephalitis, disseminated;
mortality rate as high as 80%.
Term
Pathogenesis of HSV I and HSV II
Definition
Entrance through mucosal cells or breaks in skin. Causes cytolytic reaction. Necrosis of tissue with inflammatory response. Cell fusion leads to direct cell to cell spread which circumvents certain Ab protection. Primary infection is often mild. Latency exists in neuronal cells. Cause of spontaneous reactivation unclear.
Term
Diagnosis of HSV I and HSV II
Definition
-Tzank test (cytology): poor sensitivity and specificity.
-Cell culture: Primary cells or MRC-5.
-Detection: CPE - Faster than adenovirus; rounding, refractile.
-Immunofluorescence or neutralization used to detect.
-Direct detection assays (PCR):
Sensitive, somewhat costly and not always available.
-Serology: Limited value, seroprevalence background is very high.
Term
Specimens used to diagnose HSV I and HSV II
Definition
Throat. CSF. Stool. Vesicular fluid.
Term
Treatment for HSV I and HSV II
Definition
Acyclovir (Nucleoside analog)
Ameliorates symptoms, not curative.
Term
Incubation period for HSV I and HSV II
Definition
3-5 days.
Term
Epidemiology of HSV I and HSV II
Definition
Worldwide. Up to 90% of adult population has HSV I Ab. Problem of vertical spread with HSV II; challenge for medical practice. Most disease is self limiting at 2-3 weeks.
Term
Symptoms of Cytomegalovirus (CMV)
Definition
Infectious mononucleosis-type syndrome - Malaise, myalgia, fever, abnormal liver function, lymphocytosis.

Congenital - CNS involvement, grow retardation, hepatosplenomegaly, microcephaly, retinitis, can be fatal (TORCH testing)

Immunocompromised - Pneumonia as a complication to systemic disease.
Term
Pathogenesis of CMV
Definition
Entrance through epithelial cells.
Causes cytomegalic reaction.
Spread very slowly in host.
Multi-organ involvement: Lung, liver, colon, kidneys, lymphocytes, salivary glands.
Can be latent.
Viral shedding in oral cavity and urine.
Term
Specimens used for diagnosis of CMV
Definition
Throat and urine.
Term
Diagnosis of CMV
Definition
- Direct detection: PCR.
- Cell culture: Human fibroblasts.
- Detection: Typical CPE - Very slow to appear (> 2 weeks)
- Serology: Limited value. Seroprevalence background is very high.
Term
Treatment of CMV
Definition
Acyclovir derivative (Nucleoside analog)
Term
Epidemiology of CMV
Definition
Worldwide. Up to 90% of adult population has CMV Ab; varies by SES. Problem of vertical spread with CMV; up to 1% of infants in US born with CMV infection. Transfusion and organ transplant as source of CMV.
Term
Incubation period of CMV
Definition
4-8 weeks.
Term
Symptoms of Epstein-Barr virus (EBV)
Definition
Infectious mononucleosis - Malaise, fatigue, fever, headache, sore throat, lympadenopathy.

Burkitt's lymphoma - Tumor of B cells.

Nasopharyngeal carcinoma - Tumor of nasopharyngeal epithelial cells.
Term
Pathogenesis of EBV
Definition
Infected through salivary contact.
Target cells are epithelial cells of pharynx and salivary glands.
With time, B cells become infected.
Conditions to cause Burkitt's lymphoma include genetic predisposition and malaria as a co-factor.
Conditions to cause nasopharyngeal carcinoma include genetic predisposition (Chinese males) and unknown enviromental co-factors; late onset.
Term
Diagnosis of EBV
Definition
Serology - Nonspecific: detection of "heterophile" antibodies which agglutinate Sheep RBCs

Serology - Specific: dectection of EBV antigens; EA and late antigens (NAs and MA). Limited value.
- Detection of antibody: VCA IgM and IgG.
Term
Treatment for EBV
Definition
Acyclovir - limited use.
Term
Epidemiology of EBV
Definition
Worldwide. Up to 90% of adult population has EBV Ab.
Term
Incubation period of EBV
Definition
4-6 weeks.
Term
Symptoms of Varicella Zoster (VZ)
Definition
- Varicella (Chickenpox): Malaise, fever, vesicular rash (centripetal), lasting ~5 days.

- Zoster (Shingles): Severe pain in concentrated area of skin (trunk, head, neck) followed by a crop of vesicles (silver dollar size).
Term
Pathogenesis of VZ
Definition
Infected through mucosal cells of upper respiratory tract or conjuctiva.
Primary infection migrates to local lymph nodes, spread systemically and seeds the liver and spleen.
Viremia involves infection of monocytes which deposit in skin and form vesicles.
Sensory nerve cells are location of latency.
Unclear what triggers reactivation.
Term
Diagnosis of VZ
Definition
Usually made on clinical grounds (symptoms)

Culture: Vesicular fluid, fibroblast cultures like MRC 5 used, IF detection more rapid than CPE.

Other options: DFA, PCR, EM.
Term
Treatment of VZ
Definition
Acyclovir (useful for zoster up to 72 hours)
VZIG - used prophylactically.
Term
Epidemiology of VZ
Definition
Worldwide. Zoster incidence is ~20% for those over age 50. VZIG used to prevent vertical transmission. Vaccine now available.
Term
Symptoms of Human Papilloma Virus (HPV)
Definition
Common warts. Laryngeal papilloma.
Venereal warts (Condyloma acuminatum)
Plantar warts.
Term
Transmission of HPV
Definition
Direct contact.
Venereal warts are sexually transmitted.
Laryngeal papilloma transmitted via passage through infected birth canal.
Term
Pathogenesis of HPV
Definition
Transmission.
Infects cells of basal layer of epithelium.
Virus particles seen in outer cells.
Cutaneous or mucosal types of infectious processes.
Term
Replicative cycle of HPV
Definition
Highly tropic for epithelial cells.
Viral DNA exists as episome in noncanceous cells but integrates into host cell DNA in cancerous cells.

Over 100 HPV types (based on DNA mapping)
- High risk for cancer (HPV 16 and 18)
- Moderate risk
- Low risk
- Benign
Term
Properties of HPV
Definition
Icosahedral. DNA, double stranded.
No envelope. Replicates in nucleus.
>100 types. Highly tropic for epithelial cells.
Term
Diagnosis of HPV
Definition
Normally made on clinical grounds.
Excision of tissue with histological examination may be necessary.
HPV does not grow in cell culture.
PCR based assays used for epidemiologic purposes.
Diagnostic procedures now available for women >30.
Supplemental to Pap smears.
Term
Treatment of HPV
Definition
Podophyllin or salicyclic acid topically.
Surgical removal.
Cryotherapy.
Term
Incubation period for HPV warts
Definition
2-3 months
Term
Epidemiology of HPV
Definition
Worldwide. ~20 million people in the US infected with HPV. ~12,000 cases of cervical cancer. Humans as reservoir. Greater than 100 types, most benign. Vaccine available for HPV 16 and 18.
Term
Symptoms for Parvovirus B19
Definition
Erythema infectiosum (Fifth Disease)
- Rash ("Slapped Cheek")
- Joint involvement with adult cases
- Clinical signs last only 2-4 days
- Mild constitutional symptoms may occur

Aplastic crisis.
Hydrops fetalis.
Term
Pathogenesis of Parvovirus B19
Definition
Assumed to be acquired via respiratory route. Targets immature erythroid cells. Therefore affects bone marrow or liver (fetal cases). Cell death occurs resulting in anemia. Neutralizing antibody is formed. Immune complexes involved in typical rash.
Term
Replicative cycle of Parvovirus B19
Definition
Highly tropic for erythroid cell line.
Binds to blood group P antigen on cell surface.
Translocation to nucleus.
Heavily dependent on host cell functions and enzymes.
Cytolytic.
Term
Properties of Parvovirus B19
Definition
Icosahedral. DNA, SINGLE stranded.
Relatively small, simple DNA virus.
No envelope. Replicates in nucleus.
Only one type (B19) causes human disease.
Highly tropic for erythroid line cells.
Term
Diagnosis of Parvovirus B19
Definition
Normally made on clinical grounds.
Serology:
- IgM assay is diagnostic.
- PCR assay for B19 is sensitive but regularly used.

Culture:
- Parvovirus does not grow well in cell culture.
Term
Treatment of Parvovirus B19
Definition
Symptomatic treatment only for erythema infectiosum.

Specific Parvovirus B19 immunoglobulin has been used for immunocompromised patients or those with severe anemia.
Term
Incubation period of Parvovirus B19
Definition
4-20 days.
Term
Epidemiology of Parvovirus B19
Definition
Widespread. Occurs as sporadic cases or outbreaks, often school associated. >90% of adults have Ab. Resistant to many antiviral agents.
Term
Symptoms of Variola (Smallpox)
Definition
High fever, malaise, headache, prostration followed by characteristic centrifugal rash (macular>papular>vesicular>pustular)

30% fatality rate.
Term
Symptoms of Vaccinia
Definition
- Ocular Vaccinia
- Generalized Vaccinia (40% fatality rate)
- Encephalitis (40% fatality rate)
Term
Pathogenesis of Variola & Vaccinia
Definition
Enters through mucosal cells of upper respiratory tract.
Enters blood stream (viremia) via lymphoid cells and RES cells.
Mouth lesions develop.
Cytoplasmic inclusions formed followed by ballooning degeneration of coalescing cells.
Scarring results.
Term
Replicative cycle of Variola & Vaccinia
Definition
Fuses with target cells.
Early transcription of viral DNA occurs inside viral capsid before uncoating.
Unique among DNA viruses in that replication takes place in cytoplasm.
Cytoplasmic inclusion bodies are in effect viral "factories"
Complex viral envelope synthesized in cell.
10,000 viral particles produced per cell.
Term
Properties of Variola and Vaccinia
Definition
Complex structure. DNA, double stranded.
Very large and complex DNA virus.
Contains >100 polypeptides.
Multilayered envelope.
Replicates in cytoplasm.
Tropic for multiple cell types.
Term
Diagnosis of Variola and Vaccinia
Definition
Culture:
- Vesicular fluid or scrapings
- Cell culture or embryonated chick eggs

Direct detection:
- EM

Serology:
- Cross-reactive with other pox viruses
Term
Treatment of Vaccinia
Definition
Vaccinia immune globulin
Term
Epidemiology of Variola/Vaccinia
Definition
Effective variola vaccine (using vaccinia virus)
Disease (Smallpox) was declared eradicated in 1980.
Vaccinia is used as "vector" vaccine for some animal disease, ex: rabies.
Other pox viruses have caused sporadic disease in humans (Monkey pox, Orf virus, Molluscum Contagiosum)
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