EBV Cases

Question 1

For EBV, what is the genomic organization? enveloped? capsid?

Answer 1

dsDNA

enveloped icosahedral

Question 2

What cells does EBV have tropism for?

Answer 2

1. lytic in epithelial cells of oropharynx

2. latent infection in B cells

Question 3

What are the malignancies associated with EBV?

Answer 3

nasopharyngeal carinoma, Burkitt lymphoma, Hodgkin disease, Non-hodgkin lymphoma, X-linked lymphoproliferative disease

Question 4

How does EBV get into the host cell?

Answer 4

The viral envelope has a proteins gp350 and gp220 that bind the Cd3 complement receptor (CD21) on the B cells, initiating endocytosis

Question 5

How do viral particles get out of the cell?

Answer 5

They bud out thorugh the membrane and then lyse the cells

Question 6

How can EBV cause a latent infection in one cell, but a lytic infection in another?

Answer 6

It’s circular genome has multiple promoters and the different cellular environments cause activation of different promoters, thus expression of different genes

Question 7

What does the EBV oncogene LMP-1 do?

Answer 7

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

Question 8

Specifically, what transcription factors are activated by the LMP-1 CD40?

Answer 8

NF-KB

Question 9

What does the EBV oncogene LMP-2 do?

Answer 9

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

Question 10

Speifically, what transcription factors are activated by LMP-2?

Answer 10

fos/jun

Question 11

What does the EBNA3C oncogene do?

Answer 11

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

Question 12

What is the classic triad of infectious mononucleosis?

Answer 12

pharyngitis, lymphadenopathy, fever (and then also splenomegaly)

Question 13

What test is diagnostic for EBV infectious mononucleosis?

Answer 13

the monospot test

Question 14

The monospot test detects what type of antibody

Answer 14

heterophile antibodies produced by polyclonal expansion of B cells

Question 15

The presence of VCA-IgM in the patient’s blood indicates a ___ infection while VCA-IgG indicates a ____ infection.

Answer 15

IgM = acute infection
IgG = previous infections

Question 16

THe presence of what type of cells on blood smear is diagnostic for EBV?

Answer 16

atypical lymphocytes (Downey cells)

Question 17

What does x-linked lymphoproliferative disease present as?

Answer 17

fulminant infectious mononucleosis

Question 18

Describe the typical presentation of fulminant infectious mononucleosis.

Answer 18

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)

Question 19

What is the molecular basis for X-linked lymphoproliferative disease? (aka…what protein is mutated)

Answer 19

it’s a mutation that results in a non-functional SAP protein

Question 20

What does SAP usually do? WHat’s lacking if you don’t have it?

Answer 20

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