Varicella Zoster Virus

Question 1

describe the VZV virion

Answer 1

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

Question 2

VZV cell cycle

Answer 2

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

Question 3

which cells do VZV infect

Answer 3

respiratory mucosal epithelial cells

Question 4

where do infected cells carry the virus

Answer 4

to tonsil T cells located in draining lymph nodes

Question 5

how do patients get the skin condition known as varicella

Answer 5

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

Question 6

how do patients develop the condition known as zoster

Answer 6

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

Question 7

how is VZV spread throughout the body

Answer 7

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

Question 8

where does VZV establish latency

Answer 8

in sensory ganglia of peripheral nervous system

Question 9

what condition results from reactivation

Answer 9

shingles, or eventually, postherpetic neuralgia

Question 10

VZV has tropism for what kind of cells

Answer 10

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

Question 11

skin-homing markers allow T cells to

Answer 11

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

Question 12

retrograde transport

Answer 12

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

Question 13

anterograde transport

Answer 13

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

Question 14

primary VZV infection is initiated in ____ cells

Answer 14

epithelial cells

Question 15

after primary infection, virus is transferred to

Answer 15

T cells in tonsils and other regional lymphoid tissue

Question 16

T cell infection with VZV enabled

Answer 16

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

Question 17

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

Answer 17

dorsal root ganglion

Question 18

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

Answer 18

satellite glia cell

Question 19

over time, VZV infection in satellite glial cells contributes to

Answer 19

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

Question 20

potential VZV complications

Answer 20

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

Question 21

laboratory diagnosis of herpes zoster: unequivocal confirmation

Answer 21

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

Question 22

rapid impression diagnosis of VZV

Answer 22

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)

Question 23

Tzanck test

Answer 23

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

Question 24

VZV differs from the other herpes viruses in that

Answer 24

assembled visions typically remain highly cell-associated

Question 25

herpes viruses

Answer 25

simplex 1 and 2, zoster, EBV, CMV, roseola 6&7, and kaposi’s sarcoma associated virus

Question 26

how does herpes simplex virus travel in the body

Answer 26

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

Question 27

EBV associated with

Answer 27

endemic Burkitt’s lymphoma, hodgkin’s disease, nasopharyngeal carcinoma, B cell lymphoma in the immunosuppressed, and hairy oral leukoplakia

Question 28

acyclovir/valacyclovir/famciclovir mode of action

Answer 28

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

Question 29

pharmacokinetics of acyclovir

Answer 29

low oral bioavailability, 15-20% reaches the plasma

Question 30

valacyclovir pharmacokinetics

Answer 30

54% of the dose is converted to acyclovir, increasing the bioavailability of acyclovir by 3-4 times than just acyclovir alone

Question 31

famciclovir pharmacokinetics

Answer 31

rapidly absorbed when given orally, reaches max concentration in about 15-20 minutes, 4-5 times the oral bioavailability of acyclovir alone

Question 32

ganciclovir mode of action

Answer 32

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

Question 33

ganciclovir pharmacokinetics

Answer 33

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

Question 34

foscarnet mode of action

Answer 34

inhibits viral DNA synthesis independent of thymidine kinase. pyrophosphate analogue interferes with the binding of pyrophosphate to its binding sate of DNA polymerase

Question 35

foscarnet pharmacokinetics

Answer 35

active against thymidine kinase deficient VZV strains, resistant to acyclovir in immunocompromised patients

Question 36

cidofovir mode of action

Answer 36

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

Question 37

cidofovir pharmacokinetics

Answer 37

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

Question 38

varivax

Answer 38

varicella virus vaccine, live attenuated

Question 39

types of vaccines for chicken pox

Answer 39

monovalent and combination

Question 40

monovalent chicken pox vaccine

Answer 40

varilix and varivax

Question 41

combination chicken pox vaccine

Answer 41

measles, mumps, and rubella as well

Question 42

adverse event of monovalent vaccine for chicken pox

Answer 42

fever, injection site reactions like rash, generalized rash, febrile seizures with MMR injection

Question 43

adverse event of combination chicken pox vaccine

Answer 43

fever, skin rash, febrile seizures in combination with MMR vaccine in small children

Question 44

zostavax

Answer 44

vaccine intended for people 60+ to prevent shingles, higher dose than varivax

Question 45

varivax (as opposed to zostavax)

Answer 45

for people who have not had chicken pox to prevent them from acquiring the infection

Question 46

stressors that can induce VZV reactivation

Answer 46

GI issues, HBP, obesity, heart disease, diabetes, poor sleep, chest pain, headaches, changes in sex drive, mood, anxiety, over/undereating, and substance abuse

Question 47

hospital admission due to VZV for patients with the following conditiosn

Answer 47

severe symptoms, immunosupression, atypical presentations, involvement of 2 or more dermatomes, significant facial superinfection, diseseminated herpes zoster, ophthalmic involvement