title: The BZLF1 homolog of an Epstein-Barr-related gamma-herpesvirus is a frequent target of the CTL response in persistently infected rhesus macaques.
abstract: Although CD8(+) T lymphocytes targeting lytic infection proteins dominate the immune response to acute and persistent EBV infection, their role in immune control of EBV replication is not known. Rhesus lymphocryptovirus (rhLCV) is a gamma-herpesvirus closely related to EBV, which establishes persistent infection in rhesus macaques. In this study, we investigated cellular immune responses to the rhLCV BZLF1 (rhBZLF1) homolog in a cohort of rhLCV-seropositive rhesus macaques. rhBZLF1-specific IFN-gamma ELISPOT responses ranging between 56 and 3070 spot-forming cells/10(6) PBMC were detected in 36 of 57 (63%) rhesus macaques and were largely mediated by CD8(+) T lymphocytes. The prevalence and magnitude of ELISPOT responses were greater in adult (5-15 years of age) rather than juvenile macaques (<5 years of age), suggesting that rhBZLF1-specific CTL increase over time following early primary infection. A highly immunogenic region in the carboxyl terminus of the rhBZLF1 protein containing overlapping CTL epitopes restricted by Mamu-A*01 and other as yet unidentified MHC class I alleles was identified. The presence of a robust CD8(+) T lymphocyte response targeting this lytic infection protein in both rhesus macaques and humans suggests that these CTL may be important for immune control of EBV-related gamma-herpesvirus infection. These data underscore the utility of the rhLCV-macaque model for studies of EBV pathogenesis.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Fogg
authors.forename: Deirdre
authors.initials: D
authors.lastname: Garry
authors.forename: Amany
authors.initials: A
authors.lastname: Awad
authors.forename: Fred
authors.initials: F
authors.lastname: Wang
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000145:classification / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006239:Haplotypes; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology; D018143:Lymphocryptovirus / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D015534:Trans-Activators / Q000145:classification / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D014764:Viral Proteins / Q000145:classification / Q000276:immunology*
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D015534:Trans-Activators; D014764:Viral Proteins