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70 Cards in this Set
- Front
- Back
What is the genome / structure of Herpesviruses?
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- dsDNA linear
- Enveloped - Tegument |
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What are the three subfamilies of Herpesviruses?
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- α - Herpes Simplex Virus (HSV-1 and -2); Varicella Zoster Virus (VZV = HHV-3)
- β - Cytomegalovirus (CMV = HHV-5), Roseolovirus (HHV-6), HHV-7 - γ - Epstein-Barr Virus (EBV = HHV-4), Kaposi's Sarcoma Virus (KSHV = HHV-8) |
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What are the α-Herpesviruses?
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HHV-1, -2, -3:
- Herpes Simplex Virus (HSV-1 and HSV-2) - Varicella Zoster Virus (VZV = HHV-3) |
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What are the β-Herpesviruses?
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HHV-5, -6, -7:
- Cytomegalovirus (CMV = HHV-5) - Roseolovirus (HHV-6) - HHV-7 (less common cause of roseola) |
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What are the γ-Herpesviruses?
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HHV-4, -8:
- Epstein-Barr Virus (EBV = HHV-4) - Kaposi's Sarcoma Virus (KSHV = HHV-8) |
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What makes a virus a Herpesvirus?
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- Encode collection of enzymes involved in nucleotide metabolism (thymidine kinase), DNA synthesis (DNA polymerase), and protein kinase
- Synthesis of viral DNA and capsid assembly in nucleus; the rest of the virion assembled in cytoplasm - Two life-cycles: lytic and latency |
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What is the purpose of viral vhs protein?
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Protein of Herpesvirus
- Virion host shut-off - Degrades host mRNA |
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What transcription factor initials herpesvirus gene transcription?
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VP16 --> localizes to nucleus
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What happens during the latent stage of Herpesvirus?
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- Immune system clears replicating virus during acute infection
- HSV maintains latency w/ occasional reactivation for life of host - Same strain persists within same host as an episome (associated w/ host neucleosomes) - Very little if any gene expression (repression of lytic genes) |
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What can re-trigger a latent Herpesvirus infection?
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- Immunocompromise
- Stress - Infections w/ other viruses - UV irradiation - Physical trauma (damage of neurons) |
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What are the differences in incidence of HSV-1 vs HSV-2?
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- Majority of U.S. adults positive for HSV-1
- 17% positive for HSV-2 (25% of females, 12.5% of males) |
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How are HSV-1 and HSV-2 transmitted?
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- HSV-1: respiratory secretions, saliva (more common from oral cavity)
- HSV-2: sexual contact, perinatal (more common from genital tract) |
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How do HSV-1 and HSV-2 infect sensory neurons? Where?
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- After primary infection there is robust replication
- May disseminate via retrograde transport to sensory ganglia where it maintains latency - HSV-1 --> trigeminal ganglia - HSV-2 --> sacral ganglia |
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How is HSV latency characterized?
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- Expression of a group of viral mRNAs called Latency Associated Transcripts (LATs) - never translated into protein
- Function to repress HSV gene expression (unknown mechanism) - Unknown stimuli trigger viral reactivation |
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What are the chances of reactivation of untreated HSV-2?
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25% on any given day
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What is meant by an exogenous re-infection?
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Reinfection of a seropositive individual with a different strain of HSV (possible but uncommon)
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How do you treat Herpesvirus (HSV-1 and HSV-2)?
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- Target replicating virus only
- No way to clear latent herpesvirus infections ** Tx of choice: Nucleoside analogs (Acyclovir) - inhibits viral but not cellular DNA synthesis - Relies on immune system to clear cells that lytically replicate herpes |
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What is the mechanism of Acyclovir?
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- Suicide inhibitor - competes w/ dGTP for VIRAL DNA polymerase
- Binds to Acyclovir irreversibly - Does not affect cellular DNA polymerase |
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What are the symptoms of HSV-1 infection?
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* Acute Herpetic Gingivostomatitis or Pharyngitis
* Herpes Labialis (cold sore) * Keratoconjunctivitis (leading cause of blindness) * Temporal lobe encephalitis - Herpes gladiatorium (dermatitis in athletes - wrestling) - Herpes whitlow (hand dermatitis - esp. health care workers - gloves don't prevent transmission) - Some genital lesions - Neonatal herpes - Latent in trigeminal ganglia |
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What are the symptoms of HSV-2 infection?
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* Herpes genitalis
* Neonatal herpes - Some oral lesions - Latent in sacral ganglia |
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What are the characteristics of Neonatal Herpes?
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- Can be caused by both HSV-1 and HSV-2
- Inoculation during birth (most common) but also during pregnancy (birth defects) - Infxn during 1st tri --> miscarriage, infxn during 2nd or 3rd tri --> birth defects - Replicating in CNS - Disease usually manifests within days of life (may not have skin lesions though - hard to diagnose) - High mortality - even w/ Acyclovir - Neurological abnormalities in survivors |
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How do you diagnose Herpesvirus (HSV-1 and HSV-2)?
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- Vesicles at site of inoculation
- Culture of virus, immunofluorescence w/ antibodies against HSV antigens, PCR assays - Serology |
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What is the causative agent of Chickenpox? How long does it incubate?
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- Varicella Zoster Virus (VZV = HHV-3)
- 10-21 days |
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How is Varicella Zoster Virus (VZV = HHV-3) spread?
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- Person-to-person contact
- Infectious even before skin lesions appear - Aerosolized both from lesions and from respiratory tract |
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Where does Varicella Zoster Virus (VZV = HHV-3) replicate?
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- T cells
- Epithelial cells - Endothelial cells - Latency in sensory nerve ganglia (dorsal root and/or trigeminal ganglia) |
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How does Varicella Zoster Virus (VZV = HHV-3) latency differ from HSV-1 and HSV-2 latency?
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In VZV, several viral gene products are actively transcribed and translated within latently infected neurons
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What are the symptoms of Varicella Zoster Virus (VZV = HHV-3) --> Chickenpox?
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- Blisters (50-300)
- Itching - Malaise - Fever - Secondary bacterial infection may occur in blisters - Secondary skin infection and pneumonia more common if primary infection during adulthood - Can be fatal in immunocompromised patients |
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How is Varicella Zoster Virus (VZV = HHV-3) infection (chickenpox or shingles) treated?
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Antivirals (acyclovir, VZV immune globulin)
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What causes Herpes Zoster?
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- Shingles
- Varicella Zoster Virus (VZV = HHV-3) reactivation of latent infection |
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What are the symptoms of Varicella Zoster Virus (VZV = HHV-3) --> Shingles / Herpes Zoster?
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- Reactivation of a single (usually) sensory ganglia --> shows up in single dermatome
- >50 yo - If in Trigeminal ganglia --> vision impairment - Complication: postherpetic neuralgia |
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What causes Postherpetic Neuralgia? Symptoms?
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- Significant complication of Herpes Zoster (Varicella Zoster Virus (VZV = HHV-3))
- Severe pain at dermatome w/o vesicular lesion - Can mimic appendicitis or a heart attack - Lasts for many months * Antivirals have no effect |
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What are important differential diagnoses for Varicella Zoster Virus?
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- Bacterial or enterovirus infections
- Contact dermatitis - Disseminated HSV - Historically, smallpox |
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What are the characteristics of the Varicella Zoster Virus (VZV = HHV-3) vaccine? Efficacy?
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- Live-attenuated virus - Oka strain
- Given to young children (2 doses) - 15-20% will get infected w/ wild-type VZV --> establishes latency - Reduces severity of primary infection - Can reactivate and cause Zoster / Shingles (milder symptoms) - Can be transmitted to immunocompromised (be careful if there are immunocompromised siblings) - Used in elderly to prevent Zoster / Shingles (>60 yo) |
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What are the β-Herpesviruses?
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HHV-5, -6, -7:
- Cytomegalovirus (CMV = HHV-5) - Roseolovirus (HHV-6) - HHV-7 (less common cause of roseola) |
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What are the γ-Herpesviruses?
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HHV-4, -8:
- Epstein-Barr Virus (EBV = HHV-4) - Kaposi's Sarcoma Virus (KSHV = HHV-8) |
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What does "Lymphotropic" Herpesvirus mean?
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- Replication in cells including lymphoid origin
- β - CMV (HHV-5) --> Monocytes and Macrophages - β - Roseolovirus (HHV-6) --> T-lymphocytes - γ - EBV (-4) and Kaposi's Sarcoma Virus (KSV, -8) --> B lymphocytes and plasma cells |
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What type of virus is Cytomegalovirus (CMV)? What cells does it replicate in? What do the infected cells look like?
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- Herpesvirus (HHV-5)
- Replicates in monocytes and macrophages - Infected cells look like "owl eyes", inclusion bodies |
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Who is infected with Cytomegalovirus (CMV) (HHV-5)?
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Associated with socio-economic condition and age:
- 40-80% in US - ≥ 90% in developing countries |
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What are the symptoms of Cytomegalovirus (CMV) (HHV-5) in healthy adults?
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- Mild mononucleosis
- Cold-like symptoms |
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What is the leading cause of congenital birth defects? Symptoms?
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- Cytomegalovirus (CMV) (HHV-5)
- Mild-to-severe retardation - Deafness and vision loss (permanent) - Death - Petechial lesions, small size, hepatosplenomegaly, jaundice - Seizures |
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What are the long-term persistent infection associations of Cytomegalovirus (CMV) (HHV-5)?
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- Atherosclerosis
- Immunosenescence |
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What is the genome / structure of Cytomegalovirus (CMV) (HHV-5)?
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- dsDNA (linear)
- Icosahedral - Tegument and envelope |
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How is Cytomegalovirus (CMV) (HHV-5) transmitted?
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Direct contact w/ virus-containing secretions:
- Sexual contact (semen, cervical secretions) - Blood (transfusion), organ transplant - Saliva, tears - Brast milk - Urine, feces Inoculation onto a mucosal site |
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Where is Cytomegalovirus (CMV) (HHV-5) most commonly transmitted?
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Daycares
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What is the immune response to Cytomegalovirus (CMV) (HHV-5)?
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- Innate: macrophages, interferon, NK cells (control but insufficient to clear)
- Humoral: limits re-infection or reactivation - CMI: cytotoxic T cells kill CMV-infected cells (up to 10% of all CD8 T cells may be directed against CMV) - Unable to completely control CMV; re-infection does occur |
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What are the symptoms of Cytomegalovirus (CMV) (HHV-5) in healthy adults and children?
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- Mild but often unapparent
- Fever, fatigue, sore throat, headache (2-3 weeks) - Subclinical hepatitis - Lymphocytosis - increase number of lymphocytes and atypical lymphocytes - Mononucleosis |
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What causes 8% of all infectious mononucleoses?
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Cytomegalovirus (CMV) (HHV-5)
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What is the diagnosis if there are "Owl's Eyes" cells in urine or other tissues?
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Cytomegalovirus (CMV) (HHV-5)
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How do you treat Cytomegalovirus (CMV) (HHV-5) infection?
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- Ganciclovir (IV) or Valganciclovir (oral) - nucleoside analog, activ. by phosphorylation (inhibits DNA pol)
- Foscarnet (IV) - pyrophosphate analog (inhibits DNA pol) - Cidofovir (IV) - nucleoside analog (inhibits DNA pol) ** Acyclovir is ineffective ** - Anti-CMV IgG (Cytogram) also given in conjunction |
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How does Cytomegalovirus (CMV) (HHV-5) infection affect immunosuppressed?
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- Life threatening
* Pneumonia * Retinitis - Fever, hepatitis, encephalitis, myelitis, colitis, uveitis, and neuropathy |
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What kind of virus is Epstein-Barr Virus?
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- γ-Herpesvirus (dsDNA)
- HHV-4 |
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What are the sites of infection with Epstein-Barr Virus (HHV-4)?
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- Replicate in B cells or epithelial cells (of pharynx)
- Latent infection in memory B cells - Stimulates and immortalizes B cells |
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How is Epstein-Barr Virus (HHV-4) transmitted?
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- Saliva (kissing disease)
- Blood - Respiratory secretions |
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What is the difference between Latency Type I/II and Type III for Epstein-Barr Virus (HHV-4)?
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- Type I/II - viral antigens in memory B cells; leads to Burkitt's, Hodgkin lymphomas, nasopharyngeal carcinoma
- Type III - viral antigens in proliferating B cells; infectious mononucleosis |
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What causes mononucleosis in Epstein-Barr Virus (HHV-4)?
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Rapid proliferation of atypical T cells (Downey Cells) - overactive immune response
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When is Epstein-Barr Virus (HHV-4) infection most common? Symptoms?
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- Puberty - 25 years old (Kissing Disease)
- 5-20% of B cells infected w/ EBV in 1st week - Fever, malaise, lymphadenopathy, exudative pharyngitis * Splenomegaly (1-4 weeks) - Due to T cell response - Asymptomatic in young children |
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What causes Post-Transplant Lympho-Proliferative Disorder (PTLD)? Incidence/prognosis?
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- Epstein-Barr Virus (HHV-4) mediated B cell proliferative disease
- Immunosuppressive therapy activates infection - 1-33% transplants depending on organ w/in 1st year after transplant - Arises in donor B cells or reactivation in recipient - Low risk if graft contains donor T cells - Poor prognosis: 40-70% mortality |
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How can you treat Post-Transplant Lympho-Proliferative Disorder (PTLD) (due to reactivation of EBV)?
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- No antiviral drugs or vaccines
- Reduce immunosuppression (which is activating latent EBV) - Make EBV-specific T cell lines from donor and infuse them |
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How can you diagnose Epstein-Barr Virus (HHV-4) besides serology, fluorescence, and PCR?
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- Test for heterophile antibodies by agglutination of animal RBCs
* Monospot test (horse RBC) = + |
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What cancers are associated with Epstein-Barr Virus (HHV-4)?
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- Burkitt's Lymphoma (B cell lymphoma of jaw and face, in children 5-10 yo; associated w/ chromosomal translocation)
- Hodgkin's Lymphoma - Nasopharyngeal epithelial carcinoma |
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Which Herpesvirus is a common cause of admittance to ER for infants? Symptoms? Where does it replicate?
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- HHV-6b (β-herpesvirus)
- dsDNA - High fever ~ 4 days, irritability, malaise, lymphadenopathy, rash (ROSEOLA) - Replicates in CD4+ T cells |
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What cancers are associated with HHV-8? Where does it replicate?
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- Kaposi's Sarcoma (γ-Herpesvirus)
- Replicates in CD19+ peripheral B cells, endothelial cells, monocytes, keratinocytes, and epithelial cells |
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What kind of humoral immunity is used against a primary EBV infection?
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Heterophile antibodies
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T/F: CMV infection can be detected by PCR and treated w/ Acyclovir?
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False - acyclovir is ineffective for CMV
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What virus causes PTLD (Post-Transplant Lympho-Proliferative Disorder)?
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EBV - Epstein-Barr Virus (HHV-4)
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Where is Cytomegalovirus (CMV) frequently contracted from?
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Daycares
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What viruses cause infectious mononucleosis?
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- EBV
- CMV |
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what is the causative agent for chickenpox/shingles? |
varicella-zoster |
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should you use aspirin to treat varicella zoster |
no, it is counter indicative as it predisposes kids to liver damage [reyes syndrome] |
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what does the vaccine Virus-Oka treat and how is it administered? how does it work? |
for varicella zoster: two doses Establishes a latent infection that has a mild re-emergence later in life compared to a wild strain. |