Varicella Zoster Virus Flashcards

1
Q

describe the VZV virion

A

lipid-rich envelop, into which viral glycoproteins are inserted, tegument layer composed of regulatory proteins, icosahdedral nucleocapsid core, linear double stranded DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

VZV cell cycle

A

attach to cell membranes, fuse, release tegument proteins, capsids dock and nuclear pores, DNA is injected and circularizes, viral gene transcription/replication occur, creating nucleocapsids, glycoproteins, and tegument proteins using cell machinery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

which cells do VZV infect

A

respiratory mucosal epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

where do infected cells carry the virus

A

to tonsil T cells located in draining lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how do patients get the skin condition known as varicella

A

infected T cells are induced to express skin homing factors, transport the virus to dermal fibroblasts and keratinocytes, produce pro inflammatory cytokines, resulting in inflamed skin cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how do patients develop the condition known as zoster

A

reactivation from latency enables a second phase of replication to occur in the skin, causing lesions in only the single dermatome that is innervated by the affected sensory ganglion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how is VZV spread throughout the body

A

enters via conjunctiva and upper respiratory tract, replicates locally in closest lymph node, travels through blood primarily via infected T cells, replicates again in visceral organs, travels again through blood and infects the skin, presenting as “chicken pox” rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

where does VZV establish latency

A

in sensory ganglia of peripheral nervous system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what condition results from reactivation

A

shingles, or eventually, postherpetic neuralgia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

VZV has tropism for what kind of cells

A

memory T cells with skin-homingg markers, these are common in the tonsils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

skin-homing markers allow T cells to

A

transport the virus across capillary endothelial cells and into the skin at the base of hair follicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

retrograde transport

A

transport from the skin to sensory neurons in the dorsal root ganglion and to the neurons of the enteric nervous system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

anterograde transport

A

following reactivation of VZV in the sensory neurons, it returns to the skin and infects the epidermis innervated by the infected neurons. Reactivation of VZV gives rise to local enteric disease such as gastric ulceration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

primary VZV infection is initiated in ____ cells

A

epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

after primary infection, virus is transferred to

A

T cells in tonsils and other regional lymphoid tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

T cell infection with VZV enabled

A

T-cell mediated spread to the skin and subsequently to dorsal root ganglion neurons by retrograde axonal transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

T-cell mediated spread can spread VZV to the skin and also to the ____

A

dorsal root ganglion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

spread of VZV to the dorsal root ganglion facilitates infection in the

A

satellite glia cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

over time, VZV infection in satellite glial cells contributes to

A

neuronal cell loss, indicated by satellite cell microproliferations referred to as nodules of nageotte

20
Q

potential VZV complications

A

ophthalmic herpes zoster, delayed contralateral hemiaresis, ramsay hunt syndrome, encephalitis, myelitis, post herpetic neuralgia

21
Q

laboratory diagnosis of herpes zoster: unequivocal confirmation

A

isolation in tissue culture, seroconversion or antibody titer, detection of DNA by PCR

22
Q

rapid impression diagnosis of VZV

A

Tzanck smear by scraping a lesion, (low sensitivity, 60%), PCR of viral DNA in vesicular fluid, immunofluorescent staining of cells from lesion or viral antigens, and immunofluorescent of antibodies to VZV membrane antigens (FAMA & ELISA, most sensitive)

23
Q

Tzanck test

A

scrape an ulcer to look for Tzanck cells, chicken pox and herpes skin test, also identifies herpes simplex, VZV, pemphigus vulgarism, and CMV

24
Q

VZV differs from the other herpes viruses in that

A

assembled visions typically remain highly cell-associated

25
herpes viruses
simplex 1 and 2, zoster, EBV, CMV, roseola 6&7, and kaposi's sarcoma associated virus
26
how does herpes simplex virus travel in the body
enters through mucosal membranes or skin breaks, replicates in the cell at the base of the lesion, infects innervating neurons, travels by retrograde transport to the ganglion
27
EBV associated with
endemic Burkitt's lymphoma, hodgkin's disease, nasopharyngeal carcinoma, B cell lymphoma in the immunosuppressed, and hairy oral leukoplakia
28
acyclovir/valacyclovir/famciclovir mode of action
phosphorylated by TK1 to acyclovir monophosphate, cellular enzymes to acyclovir diphosphate, and triphosphate. Triphosphate is a competitive inhibitor of viral DNA synthesis and acts as a chain terminator
29
pharmacokinetics of acyclovir
low oral bioavailability, 15-20% reaches the plasma
30
valacyclovir pharmacokinetics
54% of the dose is converted to acyclovir, increasing the bioavailability of acyclovir by 3-4 times than just acyclovir alone
31
famciclovir pharmacokinetics
rapidly absorbed when given orally, reaches max concentration in about 15-20 minutes, 4-5 times the oral bioavailability of acyclovir alone
32
ganciclovir mode of action
synthetic analogue of 2' deoxy guanosine, converted to ganciclovir triphosphate by cellular kinases, inhibits deoxyguanosine triphosphate incorporation into DNA, preferentially inhibiting viral DNA polymerase more than cellular DNA polymerases. Serves as a poor substrate for chain elongation, thereby disrupting viral DNA by a second route
33
ganciclovir pharmacokinetics
very limited oral absorption, about 5% fasting and 8% with food, 90% eliminated through the urine, half life 2-6 hours, depending on renal function
34
foscarnet mode of action
inhibits viral DNA synthesis independent of thymidine kinase. pyrophosphate analogue interferes with the binding of pyrophosphate to its binding sate of DNA polymerase
35
foscarnet pharmacokinetics
active against thymidine kinase deficient VZV strains, resistant to acyclovir in immunocompromised patients
36
cidofovir mode of action
monophosphate nucleotide analogue, undergoes cellular phosphorylation to diphosphate, inhibitis incorporation of deoxycytidine triphosphate into DNA. Not phosphorylated by a viral kinase, unlike other nucleoside analogues
37
cidofovir pharmacokinetics
over 80% is excreted in the urine, half live of 2-3 hours, however, the metabolite, cidofovir diphosphate, is eliminated slowly, with a half life of 24 hours first phase and 65 hours second phase, permitting it to only be dosed every 2 weeks
38
varivax
varicella virus vaccine, live attenuated
39
types of vaccines for chicken pox
monovalent and combination
40
monovalent chicken pox vaccine
varilix and varivax
41
combination chicken pox vaccine
measles, mumps, and rubella as well
42
adverse event of monovalent vaccine for chicken pox
fever, injection site reactions like rash, generalized rash, febrile seizures with MMR injection
43
adverse event of combination chicken pox vaccine
fever, skin rash, febrile seizures in combination with MMR vaccine in small children
44
zostavax
vaccine intended for people 60+ to prevent shingles, higher dose than varivax
45
varivax (as opposed to zostavax)
for people who have not had chicken pox to prevent them from acquiring the infection
46
stressors that can induce VZV reactivation
GI issues, HBP, obesity, heart disease, diabetes, poor sleep, chest pain, headaches, changes in sex drive, mood, anxiety, over/undereating, and substance abuse
47
hospital admission due to VZV for patients with the following conditiosn
severe symptoms, immunosupression, atypical presentations, involvement of 2 or more dermatomes, significant facial superinfection, diseseminated herpes zoster, ophthalmic involvement