B3.012 Prework 1 VZV Biology and Pathogenesis Flashcards
what is VZV?
varicella zoster virus
chickenpox
characterize the properties of VZV
71 ORFs lipid rich envelope into which viral glycoproteins are inserted tegument layer icosahedral nucleocapsid core linear dsDNA genome
what is a tegument?
predominantly composed of viral regulatory proteins
matrix between nucleocapsid and envelope
describe the VZV cell cycle
- enveloped VZV particles attach to cell membranes, fuse and release tegument proteins
- capsids dock at nuclear pored where genomic DNA is injected into the nucleus and circularizes
- viral gene transcription and replication occur in the nucleus
- nucleocapsids are assembled and package newly synthesized genomic DNA
- capsids enter the cytoplasm and virion glycoproteins mature in the trans Golgi region and tegument proteins assemble in vesicles
what form of VZV can be transmitted?
aerosolized
what types of cells carry VZV to the resident T cells?
infected Langerhans cells
mucosal cells
plasmacytoid dendritic cells
where are resident T cells located?
draining lymph nodes
why do “chicken pox” develop on the skin?
infected T cells are induced to express skin homing factors
transport virus to dermal fibroblasts and keratinocytes
produce pro-inflammatory cytokines resulting in vesicles
what part of the sensory nervous system terminates in the skin?
afferent fibers
what components of the nervous system can varicella vesicles directly access?
dorsal root ganglia
cranial nerve ganglia
autonomic nervous system ganglia
what enables a second phase of replication to occur in skin?
reactivation from latency
causes lesion in the dermatome innervated by the affected sensory ganglion
where does VZV enter?
conjunctiva and upper respiratory tract
where does VZV replication occur?
regional lymph nodes
what is the mechanism behind viremia?
infected T cells
what follows the primary viremia of VZV?
replication in visceral organs
when does secondary viremia occur and what is the result?
14 days after contact
acute infection of skin and chicken pox rash
where is VZV latency established?
sensory ganglia of PNS
what is the reactivation of VZV called?
shingles
postherpetic neuralgia
what types of cells are affected following VZV incolulation/replication in respiratory cells?
tonsil T cells
how do T cells traffic into and out of tonsils?
through squamous epithelial cells that line tonsillar crypts
why type of cells does VZV have an increased tropism for?
activated memory T cells that have skin homing markers
common in tonsils
how are tonsil T cells with skin homing markers relevant in VZV?
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
retrograde transport
transport from the skin to the sensory neurons in the dorsal root ganglion and to the neurons of the enteric nervous system
anterograde transport
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
what are 2 ways VZV can spread to dorsal root ganglia?
- T cell mediated spread directly to DRG
2. T cell mediated spread to skin and subsequent retrograde axonal transport to DRG
what type of neuron cell bodies can VZV access?
nociceptive
mechanoreceptive
what is the result of contiguous spread with viral transfer into new neuronal cell bodies?
amplifies opportunities for VZV delivery to skin sites of replication
over time, neuronal cell loss
indicated by satellite cell microproliferations
nodules of Nageotte
satellite cell microproliferations
what are potential complications associated with VZV?
ophthalmic herpes zoster delayed contralateral hemiparesis Ramsay Hunt syndrome encephalitis myelitis post herpetic neuralgia
why might it be difficult to diagnose herpes zoster?
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
how can unequivocal confirmation of VZV diagnosis be obtained
- isolation of VZV in susceptible tissue culture cell lines
- seroconversion or a fourfold or greater rise in Ab titer between acute phase and convalescent phase
- detection of VZV DNA by PCR
rapid impression VZV testing
- Tzanck smear
- PCR for detection of viral DNA in vesicular fluid
- immunofluorescent staining of cells from the lesion base or detection of viral antigens by assay
most frequently employed serologic tools for assessing host response to VZV
immunofluorescent detection of antibodies to VZV membrane antigens aka fluorescent antibody to membrane antigen (FAMA)
immune adherence hemagglutinin
ELISA
what is a Tzanck smear
scraping the base of the lesions in an attempt to demonstrate multinucleated giant cells
sens. 60%
how does VZV differ from other herpes viruses?
assembled virions typically remain highly cell associated
fusion of infected and uninfected cells by viral glycoproteins produce multinucleated prokaryotes
how does herpes simplex virus (HSV1-2) infect?
through mucosal membranes or breaks in the skin
where does the HSV 1-2 virus replicate?
in the cells at the base of the lesion
infects the innervating neuron
travels by retrograde transport to ganglion
epidemiology of HSV
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
natural HSV disease manifestations in humans
HSV encephalitis cutaneous ulcers genital ulcers oral mucosa (herpes labialis) corneal disease (keratitis)
herpetic whitlow
infection of fingers by HSV
health care professionals at risk
characterize EBV (HHV-4)
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
briefly describe the EBV life cycle and pathogenesis
virus entry in buccal cavity
oropharyngeal mucosa infection
lymph node germinal center differentiation
peripheral circulation
characterize CMV (HHV-5)
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
CMV pathology
cell enlargement with intranuclear inclusions
cytomegalia in viscera and parotid glands
immune suppressed end organ CMV diseases
encephalitis
retinitis
pneumonia
gastroenteritis
diseases to which CMV is a contributing factor
glioblastoma
atherosclerosis
consequences of congenital CMV passed to fetus through placenta
deafness
mental retardation
characterize Roseola viruses (HHV 6-7)
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
