B3.012 Prework 1 VZV Biology and Pathogenesis

Question 1

what is VZV?

Answer 1

varicella zoster virus

chickenpox

Question 2

characterize the properties of VZV

Answer 2

71 ORFs
lipid rich envelope into which viral glycoproteins are inserted
tegument layer
icosahedral nucleocapsid core
linear dsDNA genome

Question 3

what is a tegument?

Answer 3

predominantly composed of viral regulatory proteins

matrix between nucleocapsid and envelope

Question 4

describe the VZV cell cycle

Answer 4

1. enveloped VZV particles attach to cell membranes, fuse and release tegument proteins
2. capsids dock at nuclear pored where genomic DNA is injected into the nucleus and circularizes
3. viral gene transcription and replication occur in the nucleus
4. nucleocapsids are assembled and package newly synthesized genomic DNA
5. capsids enter the cytoplasm and virion glycoproteins mature in the trans Golgi region and tegument proteins assemble in vesicles

Question 5

what form of VZV can be transmitted?

Answer 5

aerosolized

Question 6

what types of cells carry VZV to the resident T cells?

Answer 6

infected Langerhans cells
mucosal cells
plasmacytoid dendritic cells

Question 7

where are resident T cells located?

Answer 7

draining lymph nodes

Question 8

why do “chicken pox” develop on the skin?

Answer 8

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

Question 9

what part of the sensory nervous system terminates in the skin?

Answer 9

afferent fibers

Question 10

what components of the nervous system can varicella vesicles directly access?

Answer 10

dorsal root ganglia
cranial nerve ganglia
autonomic nervous system ganglia

Question 11

what enables a second phase of replication to occur in skin?

Answer 11

reactivation from latency

causes lesion in the dermatome innervated by the affected sensory ganglion

Question 12

where does VZV enter?

Answer 12

conjunctiva and upper respiratory tract

Question 13

where does VZV replication occur?

Answer 13

regional lymph nodes

Question 14

what is the mechanism behind viremia?

Answer 14

infected T cells

Question 15

what follows the primary viremia of VZV?

Answer 15

replication in visceral organs

Question 16

when does secondary viremia occur and what is the result?

Answer 16

14 days after contact

acute infection of skin and chicken pox rash

Question 17

where is VZV latency established?

Answer 17

sensory ganglia of PNS

Question 18

what is the reactivation of VZV called?

Answer 18

shingles

postherpetic neuralgia

Question 19

what types of cells are affected following VZV incolulation/replication in respiratory cells?

Answer 19

tonsil T cells

Question 20

how do T cells traffic into and out of tonsils?

Answer 20

through squamous epithelial cells that line tonsillar crypts

Question 21

why type of cells does VZV have an increased tropism for?

Answer 21

activated memory T cells that have skin homing markers

common in tonsils

Question 22

how are tonsil T cells with skin homing markers relevant in VZV?

Answer 22

programmed for immune surveillance
can transport the virus across capillary endothelial cells into skin
microvasculature extensive at base of hair follicles
initial VZV replication observed here

Question 23

retrograde transport

Answer 23

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

Question 24

anterograde transport

Answer 24

following reactivation of VZV in sensory neurons
returns to skin and infects epidermis innervated by the infected neurons
reactivation of VZV within neurons of the ENS gives rise to local enteric disease

Question 25

what are 2 ways VZV can spread to dorsal root ganglia?

Answer 25

1. T cell mediated spread directly to DRG | 2. T cell mediated spread to skin and subsequent retrograde axonal transport to DRG

Question 26

what type of neuron cell bodies can VZV access?

Answer 26

nociceptive | mechanoreceptive

Question 27

what is the result of contiguous spread with viral transfer into new neuronal cell bodies?

Answer 27

amplifies opportunities for VZV delivery to skin sites of replication over time, neuronal cell loss indicated by satellite cell microproliferations

Question 28

nodules of Nageotte

Answer 28

satellite cell microproliferations

Question 29

what are potential complications associated with VZV?

Answer 29

``` ophthalmic herpes zoster delayed contralateral hemiparesis Ramsay Hunt syndrome encephalitis myelitis post herpetic neuralgia ```

Question 30

why might it be difficult to diagnose herpes zoster?

Answer 30

absence of rash confusion w herpes simplex, impetigo, contact dermatitis, folliculitis, scabies...etc children, young adults, and people with compromised immune systems more likely to have atypical presentations

Question 31

how can unequivocal confirmation of VZV diagnosis be obtained

Answer 31

1. isolation of VZV in susceptible tissue culture cell lines 2. seroconversion or a fourfold or greater rise in Ab titer between acute phase and convalescent phase 3. detection of VZV DNA by PCR

Question 32

rapid impression VZV testing

Answer 32

1. Tzanck smear 2. PCR for detection of viral DNA in vesicular fluid 3. immunofluorescent staining of cells from the lesion base or detection of viral antigens by assay

Question 33

most frequently employed serologic tools for assessing host response to VZV

Answer 33

immunofluorescent detection of antibodies to VZV membrane antigens aka fluorescent antibody to membrane antigen (FAMA) immune adherence hemagglutinin ELISA

Question 34

what is a Tzanck smear

Answer 34

scraping the base of the lesions in an attempt to demonstrate multinucleated giant cells sens. 60%

Question 35

how does VZV differ from other herpes viruses?

Answer 35

assembled virions typically remain highly cell associated | fusion of infected and uninfected cells by viral glycoproteins produce multinucleated prokaryotes

Question 36

how does herpes simplex virus (HSV1-2) infect?

Answer 36

through mucosal membranes or breaks in the skin

Question 37

where does the HSV 1-2 virus replicate?

Answer 37

in the cells at the base of the lesion infects the innervating neuron travels by retrograde transport to ganglion

Question 38

epidemiology of HSV

Answer 38

``` lifelong infection recurrent diseases is source of contagion asymptomatic shedding transmitted orally, sexually, into eye, breaks in skin HSV-1 = oral HSV-2 = sexual 90% have antibody by age 2 HSV2 later in life w sex ```

Question 39

natural HSV disease manifestations in humans

Answer 39

``` HSV encephalitis cutaneous ulcers genital ulcers oral mucosa (herpes labialis) corneal disease (keratitis) ```

Question 40

herpetic whitlow

Answer 40

infection of fingers by HSV | health care professionals at risk

Question 41

characterize EBV (HHV-4)

Answer 41

heterophile antibody positive infectious mononucleosis associated w Burkitts lymphoma, Hodgkins disease, nasopharyngeal carcinoma, B-cell lymphomas in patients w immunodeficiency hairy oral leukoplakia mitogen for B cells immortalizes them

Question 42

briefly describe the EBV life cycle and pathogenesis

Answer 42

virus entry in buccal cavity oropharyngeal mucosa infection lymph node germinal center differentiation peripheral circulation

Question 43

characterize CMV (HHV-5)

Answer 43

beta herpesvirus dsDNA largest virus to infect humans not highly contagious contracted from close personal contact with people who excrete the virus in body fluids can also be shed from throat and uterine cervix

Question 44

CMV pathology

Answer 44

cell enlargement with intranuclear inclusions | cytomegalia in viscera and parotid glands

Question 45

immune suppressed end organ CMV diseases

Answer 45

encephalitis retinitis pneumonia gastroenteritis

Question 46

diseases to which CMV is a contributing factor

Answer 46

glioblastoma | atherosclerosis

Question 47

consequences of congenital CMV passed to fetus through placenta

Answer 47

deafness | mental retardation

Question 48

characterize Roseola viruses (HHV 6-7)

Answer 48

spread via saliva irritable, diarrhea, cough, fever for 3-7 days as fever resolves faint macules develop on trunk and extremities that blanch upon pressure rash resolves in 1-2 days