Translation efficiency of EBNA1 encoded by lymphocryptoviruses influences endogenous presentation of CD8+ T cell epitopes.
Lymphocryptoviruses (LCV) that infect humans and Old World primates display a significant degree of genetic identity. These viruses use B lymphocytes as primary host cells to establish a long-term latent infection and express highly homologous latent viral proteins. Of particular interest is the expression of the EBV-encoded nuclear antigen-1 (EBNA1), which plays a crucial role in maintaining the viral genome in B cells. Using human and Old World primate homologues of EBNA1, we show that the internal repeat sequences differentially influence their in vitro translation efficiency. Although the glycine-alanine repeat domain of human LCV (EBV) EBNA1 inhibits its self-synthesis, the repeat domains within the simian LCV homologues of EBNA1 do not inhibit self-synthesis. As a consequence, simian LCV EBNA1-expressing cells are more efficiently recognized by virus-specific CTL when compared to human EBV EBNA1, even though both proteins are highly stable in B cells. Interestingly, we also show that similar to human EBNA1, CD8+ T cell epitopes from simian LCV EBNA1 are predominantly derived from newly synthesized protein rather than the long-lived pool of stable protein. These observations provide additional evidence that supports the theory that immune recognition of EBNA1 can occur without compromising the biological maintenance function of this protein.
Tellam
Judy
J
Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Clive Berghofer Cancer Research Centre, Queensland Institute of Medical Research, Brisbane, Australia.
Rist
Michael
M
Connolly
Geoff
G
Webb
Natasha
N
Fazou
Chrysa
C
Wang
Fred
F
Khanna
Rajiv
R
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D018143:Lymphocryptovirus / Q000276:immunology*; D014176:Protein Biosynthesis; D014162:Transfection
D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1