#13 Neurotropic Herpes Flashcards by Meghan May

General on herpseviruse
size:
genome:
enveloped?

Large dsDNA icosahedral

enveloped and tegumented

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Types of herpes simplex virus

HHV-1 (more common)

and HHV-2 (alpha)

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Longevetiy of herpse

lasts 2 hours on skin
4 on plastics
doesn’t do well outside host

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Varicella Zoster Virus (VZV)

Short replication cycle, latency mostly in sensory ganglia, broader host ranges

HHV-3

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HHV-3

Varicella zoster virus (herpesvirus)
shorter replication
latent in sensory gang
broad host

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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

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Synthesis of viral DNA and capsid assembly occur in the ______ while the rest of the virion is put together in _______

nucleus

cytoplams

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Herpese virus has:

lytic and latent stages

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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

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→ 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

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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

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Latent: Circular viral DNA associated with host nucleosomes (viral chromatin) and maintaned as______→

episome

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Latantly: very little viral gene expression (most lytic genes are trnascriptionally suppressed via viral ________→ poorly defined mechanisms trigger reactivation

chormatin- assocated histones

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REactivation of herpes?

physiological triggers of reactivation:alterations in immune system (stress or drug therapies)

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US population; majority are seropositive for _____and 17% seropositive for _____
1 in 4 females) and (1 in 8 males)

HSV-1

HSV-2

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resevroius of herpes

humans only

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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

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HSV-1 more commonly shed from

HSV-2 more commonly from

oral cavity

genital tract

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Virus transmitted to mucosa or abraded epithelium→ get robust LYTIC replication=

Primary infection

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HSV may_____ systemically and seed to several organs (adrenals, liver, CNS)

disseminate

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Virsus infects sensory neurons innervating site of inoculation—______transport to sensory ganglia = LATENTCY

retrograde

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site for latent HSV-1 =

latent HSV-2=

trigeminal

sacral

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Latency: characterized by expression of viral mRNA called __________

LATs (Latency Asociated Transcripts)

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LATs are_______ translated into protein and fnx to prepress HSV gene expression

NERVER

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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

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. 1 million/year in US and more common over ___ 2. reactivaiton w/in_______l gang may lead to vision impariment 3. 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