title: Translation efficiency of EBNA1 encoded by lymphocryptoviruses influences endogenous presentation of CD8+ T cell epitopes.
abstract: 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.
authors.affiliation: 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.
authors.forename: Judy
authors.initials: J
authors.lastname: Tellam
authors.forename: Michael
authors.initials: M
authors.lastname: Rist
authors.forename: Geoff
authors.initials: G
authors.lastname: Connolly
authors.forename: Natasha
authors.initials: N
authors.lastname: Webb
authors.forename: Chrysa
authors.initials: C
authors.lastname: Fazou
authors.forename: Fred
authors.initials: F
authors.lastname: Wang
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: 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
chemical_list: D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1