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37 Cards in this Set
- Front
- Back
Key difference between Herpes simplex and varicella zoster virus
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Varicella is more disseminated infection; herpes more localized
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Describe the structure of the HSV
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linear ds DNA with capsid, surrounded by tegument, which is further surrounded by a lipid envelope + glycoprotein spikes
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Alpha herpes virus
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HSV1, HSV2, Varicella-zoster
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Beta herpes virinae
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CMV and HHV6b (slapped cheek disease)
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Gamma herpes virus
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Kaposi's sarcoma herpes and Epstein-Barr virus
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General concepts about alpha-herpes viruses
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-acute primary infection (neonates susceptible to sepsis-like)
-latency (like DRG and trigeminal ganglion) -Disease from reactivation from latency -Primary and reactivated more severe with immunosuppressed individuals |
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Mechanisms of pathogenesis for alpha-herpes
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-cell killing from virus replication
-sepsis, systemic inflammatory response -immune-mediated disease (corneal scarring) |
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Epidemiology for alpha-herpes virus
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-no seasonal occurrence
-vast occur by adolescence -Transmission by respiratory (VZV); saliva, lesion contact or sexual activity (HSV1 and HSV2) -Spread of HSV-1 helped by high incidence of asymptomatic shedding |
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Differences between HSV-1 and HSV-2
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HSV1 in orofacial, HSV2 in genitals
75% are HSV-1 seropositive, 25% HSV-2 |
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Herpes replication cycle initial replication found where?
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-nucleated cells of mucosal epithelium of oropharynx or genitals
-follows breaks in keratinized epithelium in cells of basal epithelium |
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How do HSV enter on a cellular level?
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Surface fusion or receptor-mediated endocytosis
-then spreads to sensory neurons for HSV/VZV |
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Where does HSV transcription and replication occur?
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nucleus
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How does herpes virus leave the nucleus?
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Into ER (gains and loses envelope)
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Where does HSV latency principally occur?
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trigeminal ganglion, sacral ganglia, or DRGs and TG
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What occurs with the viral DNA when the virus reaches the neuronal cell bodies?
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limited replication, stable circular episome
-basically doesn't appear |
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What triggers reactivation of herpes virus?
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Who knows
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Worst case retrograde spread of HSV can lead to...
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encephalitis
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Factors involved in maintenance of neuronal HSV latency
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epigenetic silencing
CD8+ T cells in vicinity Viral non-coding RNAs that don't encode proteins (suppress expression of regulatory proteins) |
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3 types of primary acute infection of HSV-1
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gingivostomatitis (sores of tongue/lips/buccal mucosa/palates)
pharyngitis w/ flu-like symptoms keratoconjunctivitis and genital infection less frequent (resolve within 1-2 weeks) |
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Herpetic whitlow is caused by what?
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HSV-1 (direct inoculation)
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Herpes gladiatorum is caused by what?
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something like wrestling, HSV-1
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Primary infection of HSV-2
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genital sores
flu-like symptoms (latent infection in sacral ganglia) |
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Responses to acute HSV infection
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Epigenetic silencing
Interferon (type I) PKR (stops eIF2alpha to inhibit protein synthesis) Proinflammatory cytokines |
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Evasion of intrinsic responses to HSV infection
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acetylation (in response to epigenetics)
Inhibits IFN transcription Inhibits PKR |
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Immune responses to HSV infection
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IFN expression, presentation of viral peptides (MHC I)
-recruit naive CD8+ and CD4+ Phagocytosis by immature monocytes -secrete IL12, bring in NK cells Infect monocytes |
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Reactivated herpes generally presents as...
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cold sores
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Dx of herpes
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pathognomonic lesions-multiple vesicular lesions on red base
Isolation from clinical material-development of cytopathic effect Serology-use ELISA to distinguish between HSV-1 and -2 Can also see multinucleated cells fused together |
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Wright-Giemsa stain is used for what?
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cytopathic effect in herpes virus
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Presentation of varicella
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mild systemic febrile illness
incubation of 21 days transmission by respiratory droplets or direct contact |
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Dissemination of varicella zoster
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Initial replication in respiratory epithelium
Viremia spreads to liver and spleen Secondary viremia transports virus to skin and repiratory mucosal sites |
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Secondary complications for varicella zoster
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secondary bacterial infections
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what is reactivated zoster linked to?
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dermatomes (DRG)
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Most frequent complication to shingles
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Post herpetic neuralgia
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tx of varicella zoster
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acyclovir (similar to guanosine)
pro-drug |
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What enzyme IDs acyclovir in viruses?
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thymidine kinase (incorporated into viral DNA, stopping replication)
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Which population is more susceptible to acyclovir resistance?
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Immunocompromised
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Most common mechanism for resistance to nucleoside analogs?
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reduced levels of thymidine kinase
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