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67 Cards in this Set

  • Front
  • Back
what virus family is varicella zoster virus a part of?
herpesviridae
what kind of vaccines are given for VZV?
1. approved in 1995: prevents both acute and latent infections for previously uninfected ppl

2. new vaccine, 2006: recommended for previously infected, older ppl to prevent shingles.
Poxviruses
largest and most complex viruses

associated w/ skin lesions
what's the most serious poxvirus?
variola
what does variola cause?
smallpox
what was the first virus to be declared eradicated by the WHO in 1979?
small pox
what was the first disease controlled by immunization
smallpox
what's vaccinia?
poxvirus descended from Jenner's original vaccine against smallpox
which poxviruses are human viruses rather than transmitted from animals?
smallpox and molluscum contagiosum
what's the structure of VZV?
same as all Herpes:
1. enveloped, icosahedral
2. tegument
3. No viral pol in virion
4. sensitive to inactivation
5. ds, linear DNA
6. large, but smallest herpesvirus
7. encodes >100 proteins, >35 in virion
what are the steps of VZV replication?
1. bind cell R, envelope fuses w/ cell membrane
2. nucleocapsid, viral proteins in tegument released into cytopl
3. nucleocapsid to nuc.memb. and genome ejected into nuc
4. genome tsc by host DdRpol and replic by vDNA pol in cell nucleus
5. viral proteins synth in cytopl and transp to nuc for assembly
6. capsids form, genome inserted, envelope at nuc memb by "budding"
7. virions accum. in golgi, modification of envelope
8. release by exocytosis/lysis
what's the difference in gene expression in lytic vs. latent VZV infections?
different genes expressed

genome NOT replicated during latentcy
what does immediate early gene expression produce in VZV?


where?
viral proteins for viral gene replication

include mRNA and tsc factors for more viral RNA

viral proteins synth in cytoplasm and transported to nucleus for assembly
what does early gene expression produce in VZV?

where?
more tsc factors and enzymes like:
viral DNA pol
thymidine kinase


in cell nucleus
how is the VZV genome replicated?
by viral DNA pol in the cell nucleus

involves many viral proteins (good Tx targets)
what does late gene expression produce in VZV? When does this take place?

where?
after genome replication, mainly structural proteins produced

in the cytoplasm, then transported to nucleus for viral assembly
where do VZV virions accumulate in the cell?

what happens there?
accumulate in Golgi apparatus

viral envelope may be modified there
how are VZV virions released?
exocytosis and lysis
where is VZV found?
worldwide, no seasonal variation
How contagious and when is VZV contagious?
very contagious before and during Sx

90% attack rate
how is VZV transmitted?
by respiratory route or contact w/ skin vesicles (think chicken pox)
who gets VZV infections?
everyone:
common childhood illness (age 5-9 yo)--textbook chickenpox
teens/adults at risk for more severe form, pneumonia
immunocompromised/newborns: at risk of life threatening complications of chickenpox
what are some life threatening complications of chicken pox seen in newborns, immunocompromised?
pneumonia
encephalitis
progressive disseminated varicella
whats a consequence of severe adult chickenpox?
pneumonia
what kind of recurrent dz are elderly/immunocompromised at risk for who have been previously infected w/ chickenpox?
herpes zoster (shingles)
post-herpetic neuralgia
where's the primary replication site of VZV?

How does it spread?
upper respiratory tract mucosa

lymphatics, blood (primary viremia) and targets reticuloendothelial cells: forms syncytia and can spread cell to cell
what is primary viremia of VZV?

what are the Sx?
when virus spreading through blood, lymph to reticuloendothelial cells

prodromal symptoms
what is secondary viremia of VZV?

Sx?
spread of virus throughout body to the skin

vesicular rash in successive crops
fever, systemic sx same time as rash
higher viral titer than primary b/c multiplication in multiple sites
where does VZV become latent?


what is the replication rate?
dorsal root ganglia

doesn't reproduce
when does VZV reactivate?

what does it cause?
when CMI reduced by age, stress, immunosuppresion
(about 10-20%)

shingles or post-herpetic neuralgia
how is the rash of chickenpox different from smallpox?
"non-synchronized":
macule to papule to vesicle to pustule to crust all seen at same time

in small pox, the rash starts on the trunk and is synchronized at each stage.
whats the pathology of VZV reactivation?
virus produced in neurons where it was latent, travel along neural pathway to skin

produces rash in dermatomal distribution

can be very painful lasting for weeks (shingles) or months (post herpetic neuralgia)
what is the effect of humoral response on VZV
can limit viremia
what is necessary to resolve chickenpox?
CMI (humoral responses only limit viremia)
what's the clinical course of chickenpox?
incubation 1-2 wks
prodromal Sx: fever, malaise
rash appears trunk 1st then on head and extremities
itching can be severe
is the rash associated w/ chickenpox only on the skin?
no, it can occur in the mouth, conjunctiva and vagina

usually assoc w/ older individuals and more sever dz
what's the problem w/ giving aspirin for chickenpox (VZV) or influenza B virus in kids?
reye's syndrome
what are some complications in normal hosts with chickenpox
adults: pnuemonia (hepatitis, encephalitis)

bacterial infections secondary to scratching
how is the dx of chickenpox made?
usually clinical
what test would be used for presumptive dx of chickenpox?

how is it done?
Tzanck smear

detect viral Ag's in skin scrapings, or specimen inoculated in cell culture
how is a presumptive lab test (tzanck smear) for VZV confirmed?
clinical dg, PCR, rise in Ab titer
what's the tx for VZV?
1. none for mild dz
2. valacyclovir limits duration and severity of Sx
3. varicella zoster Ig (VZIG) can protect immunosuppressed pts from severe dz, but not during active case
what can be done to protect immunocompromised pts from severe VZV infection?
VZIG, but cant be given during active infection
what are some classic childhood rashes? which are caused by herpesviruses?
roseola (herpes)
chickenpox (herpes)
measles
parvovirus
fifth disease
can chickenpox be serious?
yes, about 12,000 ppl/yr hospitalized in US
what's the vaccine for VZV?
1. live, attenuated (Varivax) given to kids >1 yo
induces humoral and CMI response
cannot prevent zoster in previously infected
avoid giving to immunocompromised or pregnant
limited protection time...

2. higher dose booster of live, attenuated vaccine (2006) for ppl >60 yo to prevent shingles
does poxvirus have an envelope?
yes, but its not required for infectivity
how tough is poxvirus?
even though it has an envelope, its virion's still highly resistant to environment, drying, disinfectants
what does a poxvirus look like?
pretty large, with complex ovoid symmetry (Brick shaped)
what surrounds the core of a poxvirus?
an outer membrane and an envelope (not req'd for infection)
what's the viral genome of poxvirus like?
huge

ds, linear DNA
what's the only known DNA virus that replicates in the cytoplasm?
poxviruses
how do poxviruses replicate
1. bind cell R and enter by fusion
2. all tsc enzymes in virion core
3. synthesize viral DNApol
4. after DNA replicates, assembly takes place in cytoplasmic factories
5. complex process to acquire an envelope
6. some bud, most through lysis
what are lateral bodies?
in core of poxvirus, may contain tsc factors
why is pox virus the "exception virus"?
1. has envelope but still resistant and doesn't need it for infection
2. replicates in the CYTOPLASM
contains DNA dependent RNA pol and DNA dep DNA pol
how is poxvirus transmitted?
source?

when is it infectious?
contact w/ active case, usually by humans (molloscum contagiosum) or farm animals (orf, monkeypox)

only active case, not infectious during incubation period
what virus causes small pox
variola
what are some strains of smallpox you can get from cows, sheep, goats?
orf
monkeypox
what's the pathogenesis of smallpox?
primary trans: close contact (respiratory aerosol, contact w/ skin lesion/fomite like bedding)

incubation 1-2 weeks--infect URT and local LNs
followed by primary viremia
then secondary targets
followed by secondary viremia (characteristic rash)
what are the secondary targets infected in smallpox?
liver, spleen, marrow, lungs

this is followed by secondary viremia
what does secondary viremia of pox virus lead to?
infection of the skin and the rash
upon recovery from smallpox, where does the virus remain latent?

what's the immunity to re-infection?
it doesn't, the virus is eliminated from the body

lifelong immunity
how are other poxviruses transmitted? what kind of disease do they cause?
trans by direct contact with lesions.

virus remains localized.
which type of immunity protects from small pox infection?
both CMI and humoral important for infection resolution
what are the clinical manifestations of smallpox?
day 4- asymptomatic viremia
day 8- 1st sign of fever
day 12-14 - rise in fever, aching pains, prostration
day 16-18 - papular rash develops, spreads to extremities, becomes vesicular, pustular (2 wks), crusts
what's the mortality associated with variola major (smallpox)
20-50% mortality
what kind of rash is seen in smallpox?
synchronized:
papular rash develops on face and spreads to extremities
becomes vesicular, pustular (2 weeks) then crusts

rash appear about 16-18 days after infection

ALL infections symptomatic