Neurotrophic viruses Flashcards
(43 cards)
structure of herpesviruses
180-200 nm diameter large genome enveloped labile in environment DNA tegument
what kinds of viruses are in the human herpesviruses alpha family?
herpes simplex virus (HSV1, 2)
varicella zoster virus (VZV)
what are the properties of alpha herpesviruses
short replication cycle
LATENCY mostly in sensory ganglia
broader host range (in laboratory, can infect mice)
defining properties of herpesviruses
genes for a collection of enzymes involved in nucleotide metabolism, DNA symthesis, protein kinase
synthesis of viral DNA and capsid assembly occur in ncuelus; rest of virion assembled in cytoplasm
lytic and latent life cycles
what initiates herpesvirus HSV1 gene transcription in the nucleus?
viral transcription factor VP16
what transcribes HSV alpha genes?
host RNA polymerase II
what triggers expression of HSV gamma genes?
viral DNA synthesis
herpesvirus is maintained how in the nucleus of host cell?
as episome
epxression when latent infec for herpesvirus?
very little is any gene expression
physiological triggers of reactivation for the herpevirus simplex virus
immunocompromised, stress, UV irradiation, physical trauma as in damage of neurons
are herpesviruses cleared?
never
prevalance of HSV1 in US population
majority are positive
reservoirs of HSV
humans only
how is HSV1 and 2 transmitted
person to person (rarely through fomites): -intrauterine (rare) -perinatal -skin-skin -genital-genital oral-genital -oral oral
virus shedding in: saliva, oral facial lesions, genital lesions and secretions
HSV1 is more commonly shed from?
oral cavity
HSV 2 is more commonly shed from?
genital tract
pathogenesis of HSV1 and 2 occurs how?
virus transmitted to mucosa or abraded epithelium
lytic replication-this is the primary infection
in some cases, can disseminate systemically
virus infects sensory neurons that innervate the site of inoculation
retrograde transport to sensory ganglia and latent there
some triggers triggers reactivation–few viral capsides go anterograde transport to site of inoculation–reinfect the epithelial cells
this reinfection can cause lesions–>spread–this is the reucrrent infection
where is HSV1 latent
trigeminal ganglia
where is HSV2 latent
sacral ganglia
What is expressed during HSV latency?
viral mRNAS called latency associated transcripts–never translated; repress HSV gene expression
rate of reactivation for HSV2
25% on any day
what is exogenous reinfection?
reinfection of a postive individual for HSV with a different strain of HSV
how to treat herpesviruses
target replicating virus only (b/c when latent, virus uses host DNA polymerase to replicate so cannot target this)
acyclovir (nucleoside analog)-treatment of choice. when lytic, uses viral DNA polymerase
rely on host immune system to clear cells that lytically replicate herpes
NO VACCINES for HSV. VZV is only herpesvirus with vaccine
How does acyclovir work?
it is phrophorylated by viral thymidine kinase
viral DNA polymerase recognizes acyclovir triphosphate as a dGTP analog and incorporates it (cellular DNA doesn’t)–the viral DNA polymerase is now tied up
