EBV Cases Flashcards
For EBV, what is the genomic organization? enveloped? capsid?
dsDNA
enveloped icosahedral
What cells does EBV have tropism for?
- lytic in epithelial cells of oropharynx
2. latent infection in B cells
What are the malignancies associated with EBV?
nasopharyngeal carinoma, Burkitt lymphoma, Hodgkin disease, Non-hodgkin lymphoma, X-linked lymphoproliferative disease
How does EBV get into the host cell?
The viral envelope has a proteins gp350 and gp220 that bind the Cd3 complement receptor (CD21) on the B cells, initiating endocytosis
How do viral particles get out of the cell?
They bud out thorugh the membrane and then lyse the cells
How can EBV cause a latent infection in one cell, but a lytic infection in another?
It’s circular genome has multiple promoters and the different cellular environments cause activation of different promoters, thus expression of different genes
What does the EBV oncogene LMP-1 do?
It functions as a constitutively active CD40, which is responsible for CD4+ T-cell dependent activation of B cells. So this causes rampant activation of the B cells
Specifically, what transcription factors are activated by the LMP-1 CD40?
NF-KB
What does the EBV oncogene LMP-2 do?
It acts as a constitutively active B cell receptor, which is responsible for antigen-dependent B cell activation, so you get more B cell activation
Speifically, what transcription factors are activated by LMP-2?
fos/jun
What does the EBNA3C oncogene do?
It binds and activates cyclin D1 complexes
this causes hyperphosphorylation of Rb
This causes activation of the E2F family of transcription factors, leading to expression of genes that control DNA replication
Ultimately, you get cell cycle progression thorugh the G1, S phase checklist
What is the classic triad of infectious mononucleosis?
pharyngitis, lymphadenopathy, fever (and then also splenomegaly)
What test is diagnostic for EBV infectious mononucleosis?
the monospot test
The monospot test detects what type of antibody
heterophile antibodies produced by polyclonal expansion of B cells
The presence of VCA-IgM in the patient’s blood indicates a ___ infection while VCA-IgG indicates a ____ infection.
IgM = acute infection IgG = previous infections
THe presence of what type of cells on blood smear is diagnostic for EBV?
atypical lymphocytes (Downey cells)
What does x-linked lymphoproliferative disease present as?
fulminant infectious mononucleosis
Describe the typical presentation of fulminant infectious mononucleosis.
usually in a young boy - 3 years old
it’s just mono that comes on super fast and doesn’t get better basically
usually deadly (average survival is 1-2 months)
What is the molecular basis for X-linked lymphoproliferative disease? (aka…what protein is mutated)
it’s a mutation that results in a non-functional SAP protein
What does SAP usually do? WHat’s lacking if you don’t have it?
It acts as a control of apoptotic cell death of activated T cells - a sort of brake on the immune response once the pathogen is gone
(It does this by binding to SLAM and activating kinases)
If you don’t have SAP, you have a deficiency in IL-4 and the immune system as no brakes
