EBV Flashcards
EBV is in what family
herpes
HHV-4
genomic organization
dsDNA
envelope?
yes
capsid symmety
icosahedral
tropism
Lytic cycle in epithelial cells of oropharynx.
Latent infections in B cells
malignancies associated w/ EBV
nasopharyngeal carcinoma Burkitt lymphoma Hodgkin disease Non-hodgin lymphoma X-linked lymphoproliferative disease
EBV gains entry to B cells and establishes infection by
The viral envelope proteins gp350/220 bind the C3d complement receptor (a.k.a. CD21); this initiates endocytosis.
The genome circularizes, and immediate early genes, early genes, and late genes are expressed in sequence.
Viral particle then bud through cellular membranes to make infectious particles.
LMP-1
functions as a constitutively active CD40. CD40 is normally responsible for CD4+ T-cell dependent activation of B cells.
in immune synapse
LMP-1 activates the NF-kB transcription factors
LMP-2
functions as a constitutively active B cell receptor. The BCR is normally responsible for antigen dependent B cell activation.
activates fos/jun and MAPK pathways
EBNA3C
functions to bind and activate cyclin D1 complexes, resulting in:
Hyperphosphorylation of retinoblastoma protein (Rb)
De-repression (i.e. activation) of E2F family transcription factors
Expression of genes that control DNA repplication
Cell cycle progression
What kinds of molecules made when cyclin D1 activated
Rb protein –> E2F –>
DHFR, TK, TS, POL, CDC2, E2F-1
classic triad of IM symptoms
pharyngitis, lymphadenopathy, fever
monospot
The Monospot test is diagnostic for EBV IM. It detects heterophile antibodies produced by polyclonal expansion of B cells.
VCA-IgM vs VCA-IgG
IgM = acute IgG = previous
The appearance of _____________________ or Downey cells in a blood smear is diagnostic for EBV.
atypical lymphocytes (spiny, not round)
heterophile antibodies
constitutively active BCR (LMP-2) –> non-specific abs
x-linked lymphoproliferative disease presents as
Fuliminant infectious mononucleosis (FIM)
Median age for FIM is 3 years old; average survival after FIM is 1-2 months
Patients who survive FIM develop lymphoproliferative disorders and dysgammaglobulinemias
molecular basis for xlinked lymphoproliferative disease
The molecular basis for X linked lymphoproliferative disease is a mutation that results in a non-functional SAP protein.
SAP protein
SH2 domain that binds phosphorylated tyrosines on SLAM - adaptor protein that recruits kinases to the immunological synapse
deficiency in IL-4 production by T-cells –> CD4H2 and B cell CSR
AICD: Activation induced cell death
SAP controls apoptotic cell death of activated T cells. This is the mechanism of stopping the immune response once the pathogen is gone.
In XLP, SAP is absent, and the immune response has ‘no brakes’.
