EBV - Skildum Flashcards
What are the “classic triad” of symptoms for infectious mononucleosis?
Lymphadenopathy
Pharyngitis
Fever
What tests and procedures are used to diagnose Epstein Barr Virus?
Monospot Test
What does the monospot test detect?
Heterophile antibodies produced by polyclonal expansion of B-cells
The presence of what in a patient’s blood indicates an acute infection?
VCA-IgM
Viral Capsid Antigen - Monoclonal Expansion
The presence of what in a patient’s blood indicates a previous infection?
VCA-IgG
Polyclonal Expansion
The appearance of what in a blood smear is diagnostic of EBV?
Atypical Lymphocytes
aka Downey Cells
What is the treatment for EBV?
Supportive
What EBV related malagnancies might the patient be at risk for?
Nasopharyngeal Carcinoma Burkitt Lymphoma Hodgkin Disease Non-Hodgkin Lymphoma X-Linked Lymphoproliferative Disease
Epstein Barr Virus: Family? Lytic/Latent? Genomic Organization? Envelope? Capsid Semmetry?
Human Herpes Virus (HHV-4 = Gamma Herpes Virus, Latent in B-Cells) Lytic in oropharynx epithelial cells dsDNA Enveloped Icosahedral
How does EBV gain entry into B-Cells?
Viral envelope proteins bind the C3d complement receptor (CD21), which initiates endocytosis
Once EBV gains access to B-Cells, how is its genome expressed?
Genome circularizes, immediate early genes, early genes, and late genes are expressed and viral particles exocytose.
What does the EBV oncogene LMP-1 function as?
Constitutively active CD40
What is CD40 normally responsible for?
CD4+ T-cell dependent activation of B-Cells
What transcription factor does LMP-1 activate?
NF-kB
increases proliferative potential
What does the EBV oncogene LMP-2 function as?
Constitutively active B-Cell Receptor
What is the BCR normally responsible for?
Antigen dependent B-Cell activation
What transcription factors does LMP-2 active?
MAPK activation of Fos/Jun
pro-proliferative factors
The EBV oncogene EBNA3C functions to bind and activate what?
Cyclin D1 Complexes
What 4 results occur when EBNA3C binds to Cyclin D1 complexes?
- Hyperphosphorylation of the RB protein
- De-repression (activation) of E2F transcription factors
- Expression of DNA replication control genes
- Cell Cycle progression
What is an example of an oncogene?
Cyclin D
gas pedal
What are examples of a tumor supressor?
p53
RB
(brake pedal)
In what way can X-linked lymphoproliferative disease manifest?
Fuliminant Infectious Mononucleosis (FIM)
- More severe, more rapid presentation that usually results in death
- Average age: 3 years, death within 1-2 months
What is the molecular basis for X-linked Lymphoproliferative Disease?
A mutation the results in a non-functional SAP protein
- SAP binds to SLAM (CD150) and they act as a dampening signal for IL-4 production when the virus is no longer present –> Less B-Cell proliferation
- SAP depletion results in deficiency of IL-4 production by T-Cells (no apoptotic cell death of activated T-cells)
- No brakes for the immune response and B-cells do not stop proliferating
- Also regulates B-cell class switching
If a patient survives Fuliminant Infectious Mononucleosis, then they develop what disorders?
Lymphoproliferative disorders and dysgammaglobulinemias