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37 Cards in this Set

  • Front
  • Back
Key difference between Herpes simplex and varicella zoster virus
Varicella is more disseminated infection; herpes more localized
Describe the structure of the HSV
linear ds DNA with capsid, surrounded by tegument, which is further surrounded by a lipid envelope + glycoprotein spikes
Alpha herpes virus
HSV1, HSV2, Varicella-zoster
Beta herpes virinae
CMV and HHV6b (slapped cheek disease)
Gamma herpes virus
Kaposi's sarcoma herpes and Epstein-Barr virus
General concepts about alpha-herpes viruses
-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
Mechanisms of pathogenesis for alpha-herpes
-cell killing from virus replication
-sepsis, systemic inflammatory response
-immune-mediated disease (corneal scarring)
Epidemiology for alpha-herpes virus
-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
Differences between HSV-1 and HSV-2
HSV1 in orofacial, HSV2 in genitals
75% are HSV-1 seropositive, 25% HSV-2
Herpes replication cycle initial replication found where?
-nucleated cells of mucosal epithelium of oropharynx or genitals
-follows breaks in keratinized epithelium in cells of basal epithelium
How do HSV enter on a cellular level?
Surface fusion or receptor-mediated endocytosis
-then spreads to sensory neurons for HSV/VZV
Where does HSV transcription and replication occur?
nucleus
How does herpes virus leave the nucleus?
Into ER (gains and loses envelope)
Where does HSV latency principally occur?
trigeminal ganglion, sacral ganglia, or DRGs and TG
What occurs with the viral DNA when the virus reaches the neuronal cell bodies?
limited replication, stable circular episome

-basically doesn't appear
What triggers reactivation of herpes virus?
Who knows
Worst case retrograde spread of HSV can lead to...
encephalitis
Factors involved in maintenance of neuronal HSV latency
epigenetic silencing
CD8+ T cells in vicinity
Viral non-coding RNAs that don't encode proteins (suppress expression of regulatory proteins)
3 types of primary acute infection of HSV-1
gingivostomatitis (sores of tongue/lips/buccal mucosa/palates)
pharyngitis w/ flu-like symptoms
keratoconjunctivitis and genital infection less frequent
(resolve within 1-2 weeks)
Herpetic whitlow is caused by what?
HSV-1 (direct inoculation)
Herpes gladiatorum is caused by what?
something like wrestling, HSV-1
Primary infection of HSV-2
genital sores
flu-like symptoms
(latent infection in sacral ganglia)
Responses to acute HSV infection
Epigenetic silencing
Interferon (type I)
PKR (stops eIF2alpha to inhibit protein synthesis)
Proinflammatory cytokines
Evasion of intrinsic responses to HSV infection
acetylation (in response to epigenetics)
Inhibits IFN transcription
Inhibits PKR
Immune responses to HSV infection
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
Reactivated herpes generally presents as...
cold sores
Dx of herpes
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
Wright-Giemsa stain is used for what?
cytopathic effect in herpes virus
Presentation of varicella
mild systemic febrile illness
incubation of 21 days
transmission by respiratory droplets or direct contact
Dissemination of varicella zoster
Initial replication in respiratory epithelium
Viremia spreads to liver and spleen
Secondary viremia transports virus to skin and repiratory mucosal sites
Secondary complications for varicella zoster
secondary bacterial infections
what is reactivated zoster linked to?
dermatomes (DRG)
Most frequent complication to shingles
Post herpetic neuralgia
tx of varicella zoster
acyclovir (similar to guanosine)
pro-drug
What enzyme IDs acyclovir in viruses?
thymidine kinase (incorporated into viral DNA, stopping replication)
Which population is more susceptible to acyclovir resistance?
Immunocompromised
Most common mechanism for resistance to nucleoside analogs?
reduced levels of thymidine kinase