EBV- Skildum

Question 1

EBV

Answer 1

dsDNA, Enveloped, icosahedral
Tropism: lytic cycle in epithelial cells of oropharynx

Latent infections in B cells

Question 2

Malignancies associated with EBV

Answer 2

• nasopharyngeal carcinoma
• Burkitt Lymphoma
• Hodgkin disease
• Non-hodgin lymphoma
• X-linked lymphoproliferative disease

Question 3

EBV lytic infection –>

Answer 3

• first infects epithelial cells (lytic infection that kills the host cell and produces new infectious EBV particles)

Question 4

Latent infection –>

Answer 4

infect a B cell –> a different pattern of gene expression produces a latent infection –> proliferation of infected B cells is increased! (polyclonal expansion)

Question 5

How does EBV get into B cells?

Answer 5

1. Viral envelope proteins gp350/220 bind to C3d complement receptor –> initiates endocytosis
2. Vesicle that virus is in merges with lysosomes and decreases pH and causes capsid proteins to disassemble and get out of cell
3. Genome circularizes and tethers itself to host genome
4. Viral particles then bud through cellular membranes to make infectious particles

Question 6

EBV genome

Answer 6

• circular with multiple promoters

- Different patterns of gene expression occur during lytic and latent infection.

Question 7

LMP-1 oncogene

Answer 7

Constitutively active CD40

CD40= responsible for CD4+ T-cell dependent activation of B cells

-expressed on surface of B cell in latent phase

Question 8

What does LMP-1 activate?

Answer 8

NF-kB –> transcription factors

Question 9

LMP-2 oncogene

Answer 9

• Constitutively active B cell receptor

- BCR is normally responsible for antigen dependent B cell activation

Question 10

What does LMP-2 activate?

Answer 10

MAPK activation –> fos/jun transcription factors

Promotes proliferation of B cells

Question 11

EBNA3C oncogene

Answer 11

-Binds and activates cyclin D1 complexes (protects it from degradation)

1. Hyperphosphorylation of Rb
2. De-repression of E2F
3. Expression of genes that control DNA repplication
4. Cell cycle progression

Question 12

Tumor Suppressor Genes?

Oncogenes?

Answer 12

– p53, Rb

Onco: E2F, Cyclin D1

Question 13

EBV triad?

Answer 13

Pharyngitis
Lymphadenopathy
Fever

Question 14

Monospot test detects…

Answer 14

Heterophile antibodies produced by polyclonal expansion of B cells

Question 15

Viral Capsid Antigen(VCA)-IgM —>

VCA-IgG —–>

Answer 15

IgM—> acute infection

IgG—-> previous infection

Question 16

What do you see in blood smear?

Answer 16

Atypical lymophocytes or Downey cells —I bet Downing found these

Question 17

X linked lymphoproliferative Disease (Duncan disease)

Answer 17

• 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

Question 18

Molecular basis for X linked lymphoproliferative disease?

Answer 18

-mutation that results in non-functional SAP protein

Question 19

Normal SAP function?

Answer 19

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!

Question 20

SAP depletion?

Answer 20

—> low IL-4 production by T cells

XLP disease with no SAP ===no brakes on immune response.

Question 21

SAP controls what?

Answer 21

-apoptotic cell death of activated T cells.

Stops the immune response once the pathogen is gone