Quantification of simian immunodeficiency virus cytotoxic T lymphocyte escape mutant viruses.
Escape from cytotoxic T-lymphocyte (CTL) pressure is common in HIV-1 infection of humans and simian immunodeficiency virus (SIV) infections of macaques. CTL escape typically incurs a fitness cost as reversion back to wild-type can occur upon transmission. We utilized sequence-specific primers and DNA probes with real-time polymerase chain reaction (PCR) to sensitively and specifically track wild-type and escape mutant viremia at the Mane-A*17-restricted SIV Gag(371379) epitope AF9 in pigtail macaques. The generation of minor escape mutant populations is detected by the real-time PCR 2 weeks earlier than observed using standard sequencing techniques. We passaged the AF9 CTL escape mutant virus into two naïve Mane-A*17-negative pigtail macaques and showed that reversion to wild-type was rapid during acute infection and then slowed considerably at later stages of the infection. These data help refine our understanding of how CTL escape mutant viruses evolve.
Loh
Liyen
L
Department of Microbiology and Immunology, University of Melbourne, Australia.
Kent
Stephen J
SJ
D000818:Animals; D015750:Genes, gag / Q000235:genetics*; D008254:Macaca nemestrina; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000821:virology*; D014766:Viremia