EBV

Question 1

EBV is in what family

Answer 1

herpes

HHV-4

Question 2

genomic organization

Answer 2

dsDNA

Question 3

envelope?

Answer 3

yes

Question 4

capsid symmety

Answer 4

icosahedral

Question 5

tropism

Answer 5

Lytic cycle in epithelial cells of oropharynx.

Latent infections in B cells

Question 6

malignancies associated w/ EBV

Answer 6

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

Question 7

EBV gains entry to B cells and establishes infection by

Answer 7

The viral envelope proteins gp350/220 bind the C3d complement receptor (a.k.a. CD21); this initiates endocytosis.

The genome circularizes, and immediate early genes, early genes, and late genes are expressed in sequence.

Viral particle then bud through cellular membranes to make infectious particles.

Question 8

LMP-1

Answer 8

functions as a constitutively active CD40. CD40 is normally responsible for CD4+ T-cell dependent activation of B cells.

in immune synapse
LMP-1 activates the NF-kB transcription factors

Question 9

LMP-2

Answer 9

functions as a constitutively active B cell receptor. The BCR is normally responsible for antigen dependent B cell activation.

activates fos/jun and MAPK pathways

Question 10

EBNA3C

Answer 10

functions to bind and activate cyclin D1 complexes, resulting in:
Hyperphosphorylation of retinoblastoma protein (Rb)
De-repression (i.e. activation) of E2F family transcription factors
Expression of genes that control DNA repplication
Cell cycle progression

Question 11

What kinds of molecules made when cyclin D1 activated

Answer 11

Rb protein –> E2F –>

DHFR, TK, TS, POL, CDC2, E2F-1

Question 12

classic triad of IM symptoms

Answer 12

pharyngitis, lymphadenopathy, fever

Question 13

monospot

Answer 13

The Monospot test is diagnostic for EBV IM. It detects heterophile antibodies produced by polyclonal expansion of B cells.

Question 14

VCA-IgM vs VCA-IgG

Answer 14

IgM = acute
IgG = previous

Question 15

The appearance of _____________________ or Downey cells in a blood smear is diagnostic for EBV.

Answer 15

atypical lymphocytes (spiny, not round)

Question 16

heterophile antibodies

Answer 16

constitutively active BCR (LMP-2) –> non-specific abs

Question 17

x-linked lymphoproliferative disease presents as

Answer 17

Fuliminant infectious mononucleosis (FIM)
Median age for FIM is 3 years old; average survival after FIM is 1-2 months
Patients who survive FIM develop lymphoproliferative disorders and dysgammaglobulinemias

Question 18

molecular basis for xlinked lymphoproliferative disease

Answer 18

The molecular basis for X linked lymphoproliferative disease is a mutation that results in a non-functional SAP protein.

Question 19

SAP protein

Answer 19

SH2 domain that binds phosphorylated tyrosines on SLAM - adaptor protein that recruits kinases to the immunological synapse

deficiency in IL-4 production by T-cells –> CD4H2 and B cell CSR

AICD: Activation induced cell death

SAP controls apoptotic cell death of activated T cells. This is the mechanism of stopping the immune response once the pathogen is gone.

In XLP, SAP is absent, and the immune response has ‘no brakes’.