EBV - Skildum

Question 1

What are the “classic triad” of symptoms for infectious mononucleosis?

Answer 1

Lymphadenopathy
Pharyngitis
Fever

Question 2

What tests and procedures are used to diagnose Epstein Barr Virus?

Answer 2

Monospot Test

Question 3

What does the monospot test detect?

Answer 3

Heterophile antibodies produced by polyclonal expansion of B-cells

Question 4

The presence of what in a patient’s blood indicates an acute infection?

Answer 4

VCA-IgM

Viral Capsid Antigen - Monoclonal Expansion

Question 5

The presence of what in a patient’s blood indicates a previous infection?

Answer 5

VCA-IgG

Polyclonal Expansion

Question 6

The appearance of what in a blood smear is diagnostic of EBV?

Answer 6

Atypical Lymphocytes

aka Downey Cells

Question 7

What is the treatment for EBV?

Answer 7

Supportive

Question 8

What EBV related malagnancies might the patient be at risk for?

Answer 8

Nasopharyngeal Carcinoma
Burkitt Lymphoma
Hodgkin Disease
Non-Hodgkin Lymphoma
X-Linked Lymphoproliferative Disease

Question 9

Epstein Barr Virus:
Family?
Lytic/Latent?
Genomic Organization?
Envelope?
Capsid Semmetry?

Answer 9

Human Herpes Virus (HHV-4 = Gamma Herpes Virus, Latent in B-Cells)
Lytic in oropharynx epithelial cells
dsDNA
Enveloped
Icosahedral

Question 10

How does EBV gain entry into B-Cells?

Answer 10

Viral envelope proteins bind the C3d complement receptor (CD21), which initiates endocytosis

Question 11

Once EBV gains access to B-Cells, how is its genome expressed?

Answer 11

Genome circularizes, immediate early genes, early genes, and late genes are expressed and viral particles exocytose.

Question 12

What does the EBV oncogene LMP-1 function as?

Answer 12

Constitutively active CD40

Question 13

What is CD40 normally responsible for?

Answer 13

CD4+ T-cell dependent activation of B-Cells

Question 14

What transcription factor does LMP-1 activate?

Answer 14

NF-kB

increases proliferative potential

Question 15

What does the EBV oncogene LMP-2 function as?

Answer 15

Constitutively active B-Cell Receptor

Question 16

What is the BCR normally responsible for?

Answer 16

Antigen dependent B-Cell activation

Question 17

What transcription factors does LMP-2 active?

Answer 17

MAPK activation of Fos/Jun

pro-proliferative factors

Question 18

The EBV oncogene EBNA3C functions to bind and activate what?

Answer 18

Cyclin D1 Complexes

Question 19

What 4 results occur when EBNA3C binds to Cyclin D1 complexes?

Answer 19

1. Hyperphosphorylation of the RB protein
2. De-repression (activation) of E2F transcription factors
3. Expression of DNA replication control genes
4. Cell Cycle progression

Question 20

What is an example of an oncogene?

Answer 20

Cyclin D

gas pedal

Question 21

What are examples of a tumor supressor?

Answer 21

p53
RB
(brake pedal)

Question 22

In what way can X-linked lymphoproliferative disease manifest?

Answer 22

Fuliminant Infectious Mononucleosis (FIM)

• More severe, more rapid presentation that usually results in death
• Average age: 3 years, death within 1-2 months

Question 23

What is the molecular basis for X-linked Lymphoproliferative Disease?

Answer 23

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

Question 24

If a patient survives Fuliminant Infectious Mononucleosis, then they develop what disorders?

Answer 24

Lymphoproliferative disorders and dysgammaglobulinemias