In vivo fitness costs of different Gag CD8 T-cell escape mutant simian-human immunodeficiency viruses for macaques.

Abstract

The kinetics of immune escape and reversion depend upon the efficiency of CD8 cytotoxic T lymphocytes (CTL) and the fitness cost of escape mutations. Escape kinetics of three simian immunodeficiency virus Gag CTL epitopes in pigtail macaques were variable; those of KP9 and AF9 were faster than those of KW9. Kinetics of reversion of escape mutant virus to wild type upon passage to naïve major histocompatibility complex-mismatched macaques also varied. Rapid reversion occurred at KP9, gradual biphasic reversion occurred at AF9, and escape mutant KW9 virus failed to revert. The fitness impact of these mutations is KP9 > AF9 > KW9. These data provide insights into the differential utility of CTL in controlling viremia.