#13 Neurotropic Herpes Flashcards
General on herpseviruse
size:
genome:
enveloped?
Large dsDNA icosahedral
enveloped and tegumented
Types of herpes simplex virus
HHV-1 (more common)
and HHV-2 (alpha)
Longevetiy of herpse
lasts 2 hours on skin
4 on plastics
doesn’t do well outside host
Varicella Zoster Virus (VZV)
Short replication cycle, latency mostly in sensory ganglia, broader host ranges
HHV-3
HHV-3
Varicella zoster virus (herpesvirus)
shorter replication
latent in sensory gang
broad host
What enZ do herpesviruses encode
Defining biological properties:
encode collection of enZ involved in nuceotide metabolism (thymidine kinase), DNA synthesis (DNA polymerase) and protein kinase
Synthesis of viral DNA and capsid assembly occur in the ______ while the rest of the virion is put together in _______
nucleus
cytoplams
Herpese virus has:
lytic and latent stages
Herpes virus starts with:
Binding and fusion→ transport DNA into______
→ viral_______ degrades host mRNA
→ viral transcription factor _______and localizes to nucleus to initiate viral gene transcription
→ Viral DNA circulizes
nucleus
vhs
VP16
→ HSV αgene transcribed by __________
ome αgene products activate __________→
some Beta genes needed for __________→
Viral DNA syntesis triggers expression of _____
host RNA polymearse II
β genes
viral DNA synthesis
γ genes
gamma products are stuctual components of______→ viral DNA packed into________
→ filled viral capsid bud through host mmbs to make mature vrion that exits the cell
virion
capsid
Latent: Circular viral DNA associated with host nucleosomes (viral chromatin) and maintaned as______→
episome
Latantly: very little viral gene expression (most lytic genes are trnascriptionally suppressed via viral ________→ poorly defined mechanisms trigger reactivation
chormatin- assocated histones
REactivation of herpes?
physiological triggers of reactivation:alterations in immune system (stress or drug therapies)
US population; majority are seropositive for _____and 17% seropositive for _____
1 in 4 females) and (1 in 8 males)
HSV-1
HSV-2
resevroius of herpes
humans only
Transmission of herpes
is by fomites common?
Transmission:
a. person-person and RARELy by fomites
b. intrauterine is rare
c. Perinatual during birth
d. Sexually: skin/skin, Gen-Gen, Oral-Gen, oral-oral
HSV-1 more commonly shed from
HSV-2 more commonly from
oral cavity
genital tract
- Virus transmitted to mucosa or abraded epithelium→ get robust LYTIC replication=
Primary infection
- HSV may_____ systemically and seed to several organs (adrenals, liver, CNS)
disseminate
Virsus infects sensory neurons innervating site of inoculation—______transport to sensory ganglia = LATENTCY
retrograde
site for latent HSV-1 =
latent HSV-2=
trigeminal
sacral
Latency: characterized by expression of viral mRNA called __________
LATs (Latency Asociated Transcripts)
LATs are_______ translated into protein and fnx to prepress HSV gene expression
NERVER
Some latent capsids subject to ________ transport with mature virions that get back to site of inocculation
ANTEROGRADE
frequency of reactivation is _____ in untreated HSV2+ people with subclincial reactivation around ______ on any given day
HIGH
25%
possible of sero+ perons with diff strain of HSV but uncomon
Exogenous Reinfection
drug of choice for activated herpes
acyclovir
inhibits vral DNA synthesis
rely on _____ to clear cells that lytically replicate herpes
immune system
any vaccines for herpes
no, just for a live attenuated one for herpes zoster
Case study of little girl with temp of 39C, abrupt onset, lack of appetite, gingivitis, vesicular lesions on lips/tongue and no day care but 4 cats at home
→ has acute herpetic gingivostomatitis;
this is the primary presentaiton and most likely HSV-1 from mom or dad. Just needs supportive care
Recurrent oral-facial infection called:
herpes labialis
Primary oral-facial infection (HSV-1 most common)
a. Causes:
herpes gingivostomatisis or pharyngitis
herpes gingivostomatisis or pharyngitis
d/t primary oral-facial infection of HSV-1
Neonatal herpse: HSV1 or 2 from mom-baby during pregnancy:
uncommon, multiple birth defects
Neonatal herpes during birth
disseminated replcation, rash/no rash, high mortatlity even when tx with acyclovir and survival has high rate mortality
tx mom prior to birth
Herpes encephalitis:
seen in old or immunocomprimsed: reactivation goes retrograde instead of antero
Herpes keratitis and conjuctivitis:
leading cuae of blindness in US bc keep reactivating
Hepes gladiotorium
dermititis of athletes in contact sports (wrestling)
-hand dermititis—significant issue for health care workers (espcially in newborn units) and cant work with newbors bc HIGLY transmissible even with gloves
Herpes whitlow
Diagnosis of herpes
Vesicles at site of inoculation
Virology lab; culture virus and see immunofluorescene usint antiBs agains HSV antiGs or PCR assay
Serology used to determine infection status
Serology used to determine
infection status
Virology lab; culture virus and see immunofluorescene usint antiBs agains _____or PCR assay
HSV antiGs
ONLY reserviour of VZV
Humans =
Causitive agent of: chickenpox:primary with incubation of 10-21 days (long time!)
Varicella-Zoster
Transmission of varicella zoster virus
person-person contact and infected pt can be contagious before skin lesions appear
Unique transmission for herpes varicella virus thats different from HSV:
virus is AEROSOLIZED both from lesions and from respiratory tract
Varicella Zoster Virus replicates in
T cells/epithelial/endothelial
Varicella Zoster Latency is maintained in
sensory nerve gang—many involved d/t systemi spread of virus
unlike HSV, VZV has several viral gene products are ________ trnascribed AND translated w/in latently infected neurons
ACTIVELY
Primary infeciton ov VZV may involve CNS—unlike HSV, neuro abnormatiles after tx are
uncommon
Variella Zoster Virus will replicate in region lymph nodes once it has been aquired via respiratory or mucus path: Has primary viremia at____ays (incubation)→ then will replicate in liver and spleen
5 d
Secondary viremia for VZV at _____and you see the pox + fever.
day 12
Patient with VZV is contagious just before lesions and fever start for about_____
7 days
primary infection w/ VZV
~ before vaccine available annual infection rate was about = to annual birth rate.
Chicken Pox:
What do we see in Primary VZV infection
See blisters (50-300), itching, malaise and fever
a. aspirin is contraindicated b/c predisposes to liver damage—Reyes syndrome b. blisters resolve w/out scar formation, some instances see secondary bacterial infection
secondary skin/ pneumonia are more common in primary affection occurs in
adulthood
________ is very rare and associated with primary infection during pregancy and multple devo defects
Neonatal VZV
Primary VZV infection can be disseminated→ leading to
fatality esp in immunocompromise pts
TX for VZV
TX: antivirals, acyclovir, VZV immunoglobulin
reactivation of latent VZV of single (most often) sensory ganglia (historicall how we mapped dermatomes)
Herpes Zoster:
Herpes zoster
- 1 million/year in US and more common over ___
- reactivaiton w/in_______l gang may lead to vision impariment
- Duration can be controlled with
50
trigeminal
antivirals; acyclovir
complication of zoster; severe pain w/out vesicular lesion, mimic appendicitis or heart attack. Antiviral have no effect
Postherpatic neuralgia:
Key differentials for Herpes zoster
Differentials include: bacterial or entervirus infection, contact dermatitis or disseminated HSV
- historically most important differential was smallpox
- Differential of acute pain preceding herpes zoster can be complicated especially prior to cutaneous eruption
Diagnosis of Herpse zoster
Clincally: VZV DNA PCR detection of the VZV antiG in lesions by immunoflourescence
Serollogy will determine immune status of individual
Vaccine for varicella herpess was _______ viurs—Oka strain was liscensed in 1995; gives us herd like protection against transmission
live attenuated
Who recieved the vaccine: yougn children, 2 doses; required in W and up to 15-20% vaccinated ind get infected w/ wild type VZV and will
establish latency
is the vaccine useless if you end up getting chicken pox
a. vaccine can sig reduce severity of primary infection
wild type VZV strain can reactivate and cauase zoster later in life in spite of immunizatin but will be mild
life long immunity
When should we be careful with the Oka virus vaccine
Oka vaccine strain can be transmitted to immunocompormised—caution when vaccinationg health children w/ immunocompromised siblings
