Virology – Microbiology Test Questions – Flashcards

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DNA Viruses
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Adenovirus.
Hepatitis B.
Herpes Simplex I.
Herpes Simplex II.
Cytomegalovirus.
Epstein Barr Virus.
Varicella Zoster.
Human Papilloma Virus.
Human Parvovirus B19.
Variola.
Vaccinia.
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Adenoviridae
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Adenovirus (DNA)
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Hepadnaviridae
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Hepatitis B (DNA)
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Herpesviridae
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Herpes Simplex I.
Herpes Simplex II.
Cytomegalovirus.
Epstein Barr Virus.
Varicella Zoster.
(DNA viruses)
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Papillomaviridae.
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Human Papilloma Virus (DNA)
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Parvoviridae
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Human Parvovirus B19 (DNA)
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Poxviridae
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Variola.
Vaccinia.
(DNA)
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Specimens for Adenovirus diagnosis
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Stool.
Urine.
Throat.
Conjunctiva.
Rectal swab.
Virus excretion may last from days to weeks.
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Treatment for Adenovirus
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No treatment.
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Incubation period for Adenovirus
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About one week.
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Transmission of Adenovirus
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Direct contact, fecal-oral route, respiratory droplets or fomites (inanimate objects capable of transmitting pathogens)
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Properties of Adenovirus
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Icosahedral. Double stranded DNA. No envelope. Has protein "fibers". Replicates in nucleus. Narrow host range. ~50 serotypes (<1/3 responsible for most disease)
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Infectious cycle of Adenovirus
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~24 hours.
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Replicative cycle of Adenovirus
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Attachment, penetration, uncoating.
Uncoating completed in the nucleus.
Virus assembly occurs in the nucleus.
100,000 virus particles per cell.
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Pathogenesis of Adenovirus
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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.
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Insidious onset.
Elevated liver enzymes. Jaundice.
Serum sickness-like syndrome:
fever, rash, polyarteritis nodosa.
Outcomes vary; HBsAg positivity.
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Symptoms of Hep. B (HBV)
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Pathogenesis of Hep B
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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.
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Replicative cycle of Hep. B
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Similar to Adenovirus. Final assembly occurs outside of nucleus.
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Properties of Hep. B
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Icosahedral. DNA, double stranded.
Enveloped. Major proteins HBsAg and HBcAg.
Replicates in nucleus through RNA intermediate.
Many different types with different host range.
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Diagnosis of Hep. B
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Serology.
Antigen - HBsAg.
Antibody - Anti-HBcAg (IgM), Anti-HBsAg, Anti-HBcAg (IgG)
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Treatment for Hep. B
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Interferon. Antivirals directed at viral replication. Surgery (transplantation).
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Incubation period for Hep. B
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2-3 months.
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Transmission of Hep. B
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Blood borne. STI.
Transfusion associated.
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Adenovirus and Hep. B are both found where?
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Worldwide.
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Vaccine for Hep. B?
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Yes.
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Structure of Herpesviridae viruses
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Large icosahedral viruses (150-200 nm)
Double stranded DNA genome.
Enveloped (Derived from nuclear membrane)
Encodes for >100 viral specific proteins.
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Biological properties of Herpesviridae viruses
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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.
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Virus replication of Herpesviridae viruses
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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)
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Disease caused by Herpesvirus 1
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HSV I (Herpes Simplex I)
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Disease caused by Herpesvirus 2
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HSV II (Herpes Simplex II)
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Disease caused by Herpesvirus 3
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Varicella-zoster virus
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Disease caused by Herpesvirus 4
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Epstein-Barr virus (EBV)
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Disease caused by Herpesvirus 5
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Cytomegalovirus (CMV)
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Disease caused by Herpesvirus 6
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HHV 6 (Human Herpesvirus 6)
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Disease caused by Herpesvirus 7
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HHV 7 (Human Herpesvirus 7)
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Disease caused by Herpesvirus 8
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Kaposi's Sarcoma HHV
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Symptoms of HSV I
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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.
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Symptoms of HSV II
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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%.
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Pathogenesis of HSV I and HSV II
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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.
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Diagnosis of HSV I and HSV II
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-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.
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Specimens used to diagnose HSV I and HSV II
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Throat. CSF. Stool. Vesicular fluid.
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Treatment for HSV I and HSV II
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Acyclovir (Nucleoside analog)
Ameliorates symptoms, not curative.
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Incubation period for HSV I and HSV II
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3-5 days.
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Epidemiology of HSV I and HSV II
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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.
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Symptoms of Cytomegalovirus (CMV)
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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.
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Pathogenesis of CMV
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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.
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Specimens used for diagnosis of CMV
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Throat and urine.
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Diagnosis of CMV
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- Direct detection: PCR.
- Cell culture: Human fibroblasts.
- Detection: Typical CPE - Very slow to appear (> 2 weeks)
- Serology: Limited value. Seroprevalence background is very high.
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Treatment of CMV
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Acyclovir derivative (Nucleoside analog)
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Epidemiology of CMV
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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.
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Incubation period of CMV
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4-8 weeks.
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Symptoms of Epstein-Barr virus (EBV)
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Infectious mononucleosis - Malaise, fatigue, fever, headache, sore throat, lympadenopathy.

Burkitt's lymphoma - Tumor of B cells.

Nasopharyngeal carcinoma - Tumor of nasopharyngeal epithelial cells.
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Pathogenesis of EBV
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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.
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Diagnosis of EBV
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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.
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Treatment for EBV
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Acyclovir - limited use.
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Epidemiology of EBV
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Worldwide. Up to 90% of adult population has EBV Ab.
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Incubation period of EBV
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4-6 weeks.
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Symptoms of Varicella Zoster (VZ)
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- 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).
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Pathogenesis of VZ
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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.
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Diagnosis of VZ
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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.
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Treatment of VZ
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Acyclovir (useful for zoster up to 72 hours)
VZIG - used prophylactically.
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Epidemiology of VZ
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Worldwide. Zoster incidence is ~20% for those over age 50. VZIG used to prevent vertical transmission. Vaccine now available.
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Symptoms of Human Papilloma Virus (HPV)
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Common warts. Laryngeal papilloma.
Venereal warts (Condyloma acuminatum)
Plantar warts.
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Transmission of HPV
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Direct contact.
Venereal warts are sexually transmitted.
Laryngeal papilloma transmitted via passage through infected birth canal.
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Pathogenesis of HPV
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Transmission.
Infects cells of basal layer of epithelium.
Virus particles seen in outer cells.
Cutaneous or mucosal types of infectious processes.
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Replicative cycle of HPV
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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
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Properties of HPV
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Icosahedral. DNA, double stranded.
No envelope. Replicates in nucleus.
>100 types. Highly tropic for epithelial cells.
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Diagnosis of HPV
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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.
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Treatment of HPV
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Podophyllin or salicyclic acid topically.
Surgical removal.
Cryotherapy.
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Incubation period for HPV warts
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2-3 months
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Epidemiology of HPV
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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.
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Symptoms for Parvovirus B19
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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.
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Pathogenesis of Parvovirus B19
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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.
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Replicative cycle of Parvovirus B19
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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.
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Properties of Parvovirus B19
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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.
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Diagnosis of Parvovirus B19
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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.
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Treatment of Parvovirus B19
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Symptomatic treatment only for erythema infectiosum.

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

30% fatality rate.
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Symptoms of Vaccinia
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- Ocular Vaccinia
- Generalized Vaccinia (40% fatality rate)
- Encephalitis (40% fatality rate)
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Pathogenesis of Variola & Vaccinia
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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.
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Replicative cycle of Variola & Vaccinia
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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.
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Properties of Variola and Vaccinia
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Complex structure. DNA, double stranded.
Very large and complex DNA virus.
Contains >100 polypeptides.
Multilayered envelope.
Replicates in cytoplasm.
Tropic for multiple cell types.
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Diagnosis of Variola and Vaccinia
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Culture:
- Vesicular fluid or scrapings
- Cell culture or embryonated chick eggs

Direct detection:
- EM

Serology:
- Cross-reactive with other pox viruses
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Treatment of Vaccinia
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Vaccinia immune globulin
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Epidemiology of Variola/Vaccinia
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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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