Widespread Sequence Variation in Epstein‐Barr Virus Nuclear Antigen 1 Influences the Antiviral T Cell Response

Abstract

Epstein-Barr virus (EBV) nuclear antigen (EBNA) 1 is perhaps the most widely studied EBV protein, because of its critical role in maintaining the EBV episome and its expression in all EBV-associated malignancies. Much of this research has focused exclusively on theEBVwild-type (wt) strain (B95-8). Sequence analysis of the gene encoding for EBNA1 in EBV isolates from 43 Caucasians has now revealed considerable EBNA1sequence divergence from theEBVwt strain in the majority of isolates from this population group. Importantly, T cell recognition of an endogenously processed HLA-B8—binding EBNA1 epitope was greatly influenced by this sequence polymorphism.