EBV part 1 Flashcards
Which herpes virus family does EBV belong to? And what other herpes virus is in this family?
gamma herpesviruses
-also includes karposis sarcoma associated herpesvirus.
What is the structure of the EBV virus?
glycoprotein envelope, protein tegument and nucleocapsid containing large dsDNA
how is EBV transmitted and what is the incubation period?
transmitted via saliva
4-6 week incubation period.
Which cells does EBV infect? Which cells is latency established in?
Infects B cells and epithelial cells
Latency established in B memory cells
What can happen if infection occurs during adolescence?
Infectious mononucleosis.
What are the 4 symptoms of mono?
fatigue, fever, sore throat, lymphadenopathy
What two complications can arise with mono?
splenomegaly, hepatic involvement
Which glycoprotein is involved in EBV infection of B cells? And what receptor on B cells does it bind?
gp350, binds to CD2/ CD21 on B cells.
What proteins make up the core fusion machinery of EBV and what do they bind to.
gp42, gH/gL and gB.
Initial binding of the former to HLA II in endosomes.
describe the two steps of B cell EBV infection.
- gp350-CD2/21 receptor-mediated endocytosis.
2. gp42, gH gL gB binding to HLA II in endosomes triggers membrane fusion and nucleocapsid release.
What receptors are likely targeted for epithelial cell EBV infection? How many stages?
integrin receptors likely targeted (avB6/8).
Only one direct step.
What parts of the core fusion machinery is required for epithelial cell infection?
gH, gL and gB.
Which structure of the tonsils (oropharyngeal lymphoepithelial barrier) does EBV target?
the epithelial cells lining the tonsilar crypts and the local circulating B cells.
What kind of B cell infection is established first?
establishes an initial latency III infection, producng growth transformed B cells.
What three groups of EBV proteins expressed in latent III, what effect on B cells?
EBNA1, 2, 3 (A,B,C) and LP.
LMP1 and 2.
BHRF1
As a result B cells are blasted and immortalised.
What kind of viral protein is BHRF1?
an anti-apoptotic protein.
What form does the latent EBV genome take?
circular genome.
What route can some of the growth transformed B cells take?
Some will enter a lytic cycle, that enable viral replication and shedding.
Gives examples of viral genes that are expressed sequentially through lytic progression.
Immediate early- TFs like BZLF1 (for expression of others)
Early, DAN replication proteins e.g. BMLF1
LAte- encodes structural proteins e.g. BLLF1
What general groups can EBV antigens belong to?
latent and lytic infection.
What are three major cellular responses against lytic primary infection?
NK cell potentially, and large CD8+ T cel response as well as a CD4+ response.
What primary responses are made against latent infection?
CD8 and CD4 responses.
What kind of infection is established following the primary immune response against EBV?
The Lat0 infection - where gene expression is switched off to evade immune recognition.
What is the only gene that is expressed during latent ) and what does it do?
EBNA1 only present in small amounts- tether viral EBV genome to host chromosome.
What can happen to these Lat0 cells?
They will periodically activate into the lytic cycle to repopulate latent B cell pool (asymptomatically)
T cells are vital for control of EBV, what happens to immunosuppressed people?
malignancy of transformed B cells.
Immunosuppressed EBV B cell malignancies? Which stages of infection is it associated with?
post transplant lymphoproliferativ disease
Hodgkin lymphoma
Burkitt lymphoma
diffuse lare B cell lymphoma
What two epithelail cell malignancies with EBV?
Whats the rare lymphoma affecting other cell populations?
What proteins associated with?
nasopharyngeal carcinoma and gastric carcinoma.
extranodal NK/T cell lymphoma
PTLD and DLBCL associated proteins?
Hodkin and nasopharyngeal carcinoma?
Burkitt?
All the proteins expressed in latency III
Latnecy II EBNA1, and LMP1 and 2 (A/B)
EBNA1 (Lat 1/0)
