PERSISTENT HEPATITIS-C VIRUS-INFECTION IN A CHIMPANZEE IS ASSOCIATED WITH EMERGENCE OF A CYTOTOXIC T-LYMPHOCYTE ESCAPE VARIANT

Hepatitis C virus (HCV) establishes a persistent infection in humans a nd chimpanzees despite the presence of virus-specific, class I major h istocompatibility complex-restricted CD8(+) cytotoxic T lymphocytes (C TLs) in the liver. The data presented here demonstrate that CTLs direc ted against a conserved epitope in the HCV nonstructural 3 protein per sist in the liver of a chronically infected chimpanzee for at least 2 years after infection. However, these CTLs did not recognize the HCV q uasi-species present in the plasma of this animal at week 16 postinfec tion or at later time points. Escape from the CTL response was facilit ated by an aspartic acid to glutamic acid (D --> E) substitution at am ino acid position 1449 in all HCV genomes that were sequenced. The res ults of this study strongly support the concept that CTL responses can select for variant viruses with an enhanced ability to persist in a h ost and have important implications for the design of vaccines against HCV.