title: CD4+ and CD8+ T-cell responses to latent antigen EBNA-1 and lytic antigen BZLF-1 during persistent lymphocryptovirus infection of rhesus macaques.
abstract: Epstein-Barr virus (EBV) infection leads to lifelong viral persistence through its latency in B cells. EBV-specific T cells control reactivations and prevent the development of EBV-associated malignancies in most healthy carriers, but infection can sometimes cause chronic disease and malignant transformation. Epstein-Barr nuclear antigen 1 (EBNA-1) is the only viral protein consistently expressed during all forms of latency and in all EBV-associated malignancies and is a promising target for a therapeutic vaccine. Here, we studied the EBNA-1-specific immune response using the EBV-homologous rhesus lymphocryptovirus (rhLCV) infection in rhesus macaques. We assessed the frequency, phenotype, and cytokine production profiles of rhLCV EBNA-1 (rhEBNA-1)-specific T cells in 15 rhesus macaques and compared them to the lytic antigen of rhLCV BZLF-1 (rhBZLF-1). We were able to detect rhEBNA-1-specific CD4(+) and/or CD8(+) T cells in 14 of the 15 animals screened. In comparison, all 15 animals had detectable rhBZLF-1 responses. Most peptide-specific CD4(+) T cells exhibited a resting phenotype of central memory (TCM), while peptide-specific CD8(+) T cells showed a more activated phenotype, belonging mainly to the effector cell subset. By comparing our results to the human EBV immune response, we demonstrate that the rhLCV model is a valid system for studying chronic EBV infection and for the preclinical development of therapeutic vaccines.
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Leskowitz
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhou
authors.forename: F
authors.initials: F
authors.lastname: Villinger
authors.forename: M H
authors.initials: MH
authors.lastname: Fogg
authors.forename: A
authors.initials: A
authors.lastname: Kaur
authors.forename: P M
authors.initials: PM
authors.lastname: Lieberman
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D018143:Lymphocryptovirus / Q000276:immunology*; D008253:Macaca mulatta; D015534:Trans-Activators / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D016207:Cytokines; D019309:Epstein-Barr Virus Nuclear Antigens; D015534:Trans-Activators; C417029:EBV-encoded nuclear antigen 1