Neurotrophic viruses Flashcards

1
Q

structure of herpesviruses

A
180-200 nm diameter
large genome
enveloped
labile in environment
DNA
tegument
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2
Q

what kinds of viruses are in the human herpesviruses alpha family?

A

herpes simplex virus (HSV1, 2)

varicella zoster virus (VZV)

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3
Q

what are the properties of alpha herpesviruses

A

short replication cycle
LATENCY mostly in sensory ganglia
broader host range (in laboratory, can infect mice)

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4
Q

defining properties of herpesviruses

A

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

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5
Q

what initiates herpesvirus HSV1 gene transcription in the nucleus?

A

viral transcription factor VP16

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6
Q

what transcribes HSV alpha genes?

A

host RNA polymerase II

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7
Q

what triggers expression of HSV gamma genes?

A

viral DNA synthesis

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8
Q

herpesvirus is maintained how in the nucleus of host cell?

A

as episome

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9
Q

epxression when latent infec for herpesvirus?

A

very little is any gene expression

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10
Q

physiological triggers of reactivation for the herpevirus simplex virus

A

immunocompromised, stress, UV irradiation, physical trauma as in damage of neurons

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11
Q

are herpesviruses cleared?

A

never

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12
Q

prevalance of HSV1 in US population

A

majority are positive

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13
Q

reservoirs of HSV

A

humans only

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14
Q

how is HSV1 and 2 transmitted

A
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

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15
Q

HSV1 is more commonly shed from?

A

oral cavity

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16
Q

HSV 2 is more commonly shed from?

A

genital tract

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17
Q

pathogenesis of HSV1 and 2 occurs how?

A

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

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18
Q

where is HSV1 latent

A

trigeminal ganglia

19
Q

where is HSV2 latent

A

sacral ganglia

20
Q

What is expressed during HSV latency?

A

viral mRNAS called latency associated transcripts–never translated; repress HSV gene expression

21
Q

rate of reactivation for HSV2

A

25% on any day

22
Q

what is exogenous reinfection?

A

reinfection of a postive individual for HSV with a different strain of HSV

23
Q

how to treat herpesviruses

A

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

24
Q

How does acyclovir work?

A

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

25
Q

what kinds of disease can HSV 1 and 2 cause?

A

primary vs recurrent mucocutaneous infections:

  • genital disease (HSV1, 2)
  • primary oral facial infec (HSV1 usually): herpes gingivostomatitis or pharyngitis
  • recurrent oral facial infections–herpes labialis

neonatal herpes

herpes encephalitis (in immunocompromised or aging-in reinfection-through transport opposite direction to CNS instead of to initial inoculation site)

herpes keratitis and conjunctivitis

herpes gladiatorium

herpes whitlow

26
Q

how do you get cold sores? and how treated?

A

when HSV 1 reinfects during periods of immunocompromised status

not really treated

27
Q

how do you get neonatal herpes?

A

inoculation during birth is the most common way

28
Q

neonatal herpes

A

disseminated replication (virus can replicate at sites other than initial inoculation site!)

CNS commonly affected

mortality high, even w/ acyclovir

29
Q

how do you prevent neonatal herpes

A

treat mother before birth

30
Q

How do you diagnose HSV1, 2?

A

vesicles at inoculation site

lab: culture, immunofluoresce w/ antibodies against HSV antigens, PCR
serology: examine infection status

31
Q

when can someone with genital herpes be shedding virus?

A

when virus reactivates; doesn’t require that symptoms be present

32
Q

reservoirs of varicella zoster

A

humans only

33
Q

how is varicella zoster spread

A

person to person contact–infected person can transmit the virus even before skin lesions appear

aerosolized from lesions and respiratory tract
also direct contact w/ skin lesions

34
Q

pathogenesis of varicella zoster

A
infects mucosa of upper RT
virus replicates in lymph nodes
primary viremia
replication in liver, spleen, other organs
comes out, secondary viremia
starts being contagious
get fever
infects skin and vesicular rash appears
35
Q

Where are varicella zoster viruses maintained in latency

A

sensory nerve ganglia-many ganglia involved

36
Q

how is varicella zoster different from HSV

A

VZV has viral gene products that are actively transcribed and translated in latently infected neurons

37
Q

diseases caused by varicella zoster

A

chickenpox
herpes zoster
postherpetic neuralgia

38
Q

prevalance of neonatal VZV

A

very rare

39
Q

treatment for varicella zoster infection

A

antivirals-acyclovir

VZV Ig

40
Q

Herpes zoster

A

reactivation of latent VZV from single sensory ganglia

41
Q

Treatment for Herpes zoster

A

duration can be controlled with antivirals like acyclovir

42
Q

postherpetic neuralgia

A

pain w/o vesicular lesions–antivirals don’t help

43
Q

diagnosis of VZV

A

DNA PCR
detect antigens by immunofluores
serology to assess immune status