EBV- Skildum Flashcards
EBV
dsDNA, Enveloped, icosahedral
Tropism: lytic cycle in epithelial cells of oropharynx
Latent infections in B cells
Malignancies associated with EBV
- nasopharyngeal carcinoma
- Burkitt Lymphoma
- Hodgkin disease
- Non-hodgin lymphoma
- X-linked lymphoproliferative disease
EBV lytic infection –>
- first infects epithelial cells (lytic infection that kills the host cell and produces new infectious EBV particles)
Latent infection –>
infect a B cell –> a different pattern of gene expression produces a latent infection –> proliferation of infected B cells is increased! (polyclonal expansion)
How does EBV get into B cells?
- Viral envelope proteins gp350/220 bind to C3d complement receptor –> initiates endocytosis
- Vesicle that virus is in merges with lysosomes and decreases pH and causes capsid proteins to disassemble and get out of cell
- Genome circularizes and tethers itself to host genome
- Viral particles then bud through cellular membranes to make infectious particles
EBV genome
- circular with multiple promoters
- Different patterns of gene expression occur during lytic and latent infection.
LMP-1 oncogene
Constitutively active CD40
CD40= responsible for CD4+ T-cell dependent activation of B cells
-expressed on surface of B cell in latent phase
What does LMP-1 activate?
NF-kB –> transcription factors
LMP-2 oncogene
- Constitutively active B cell receptor
- BCR is normally responsible for antigen dependent B cell activation
What does LMP-2 activate?
MAPK activation –> fos/jun transcription factors
Promotes proliferation of B cells
EBNA3C oncogene
-Binds and activates cyclin D1 complexes (protects it from degradation)
- Hyperphosphorylation of Rb
- De-repression of E2F
- Expression of genes that control DNA repplication
- Cell cycle progression
Tumor Suppressor Genes?
Oncogenes?
– p53, Rb
Onco: E2F, Cyclin D1
EBV triad?
Pharyngitis
Lymphadenopathy
Fever
Monospot test detects…
Heterophile antibodies produced by polyclonal expansion of B cells
Viral Capsid Antigen(VCA)-IgM —>
VCA-IgG —–>
IgM—> acute infection
IgG—-> previous infection
What do you see in blood smear?
Atypical lymophocytes or Downey cells —I bet Downing found these
X linked lymphoproliferative Disease (Duncan disease)
- Fuliminant infectious mono (FIM)
- Median age for FIM is 3 yrs old
- survival after FIM is 1-2 months
- Survivors develop lymphoproliferative disorder and dysgammaglobulinemias
Molecular basis for X linked lymphoproliferative disease?
-mutation that results in non-functional SAP protein
Normal SAP function?
Its SH2 domain binds phosphorylated tyrosines on SLAM
-SAP is an adapter protein that recruits kinases to immunological synapse
Tells T cell to produce IL-4 IL-4 signals CD4H2 differentiation and regulates B cell class switching!
SAP depletion?
—> low IL-4 production by T cells
XLP disease with no SAP ===no brakes on immune response.
SAP controls what?
-apoptotic cell death of activated T cells.
Stops the immune response once the pathogen is gone
