The BZLF1 homolog of an Epstein-Barr-related gamma-herpesvirus is a frequent target of the CTL response in persistently infected rhesus macaques

J Immunol. 2006 Mar 15;176(6):3391-401. doi: 10.4049/jimmunol.176.6.3391.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Haplotypes
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / virology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology
  • Lymphocryptovirus / immunology*
  • Macaca mulatta / immunology*
  • Macaca mulatta / virology*
  • Molecular Sequence Data
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology
  • Trans-Activators / classification
  • Trans-Activators / immunology*
  • Tumor Virus Infections / immunology*
  • Tumor Virus Infections / virology
  • Viral Proteins / classification
  • Viral Proteins / immunology*

Substances

  • BZLF1 protein, Herpesvirus 4, Human
  • DNA-Binding Proteins
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Trans-Activators
  • Viral Proteins