Extraepitopic compensatory substitutions partially restore fitness to simian immunodeficiency virus variants that escape from an immunodominant cytotoxic-T-lymphocyte response |
| |
Authors: | Friedrich Thomas C Frye Christopher A Yant Levi J O'Connor David H Kriewaldt Nancy A Benson Meghan Vojnov Lara Dodds Elizabeth J Cullen Candice Rudersdorf Richard Hughes Austin L Wilson Nancy Watkins David I |
| |
Affiliation: | Wisconsin National Primate Research Center, Madison, Wisconsin 53715, USA. |
| |
Abstract: | Selection for escape mutant immunodeficiency viruses by cytotoxic T lymphocytes (CTL) has been well characterized and may be associated with disease progression. CTL epitopes accrue escape mutations at different rates in vivo. Interestingly, certain high-frequency CTL do not select for escape until the chronic phase of infection. Here we show that mutations conferring escape from immunodominant CTL directed against an epitope in the viral Gag protein are strongly associated with extraepitopic mutations in gag in vivo. The extraepitopic mutations partially restore in vitro replicative fitness of viruses bearing the escape mutations. Constraints on epitope sequences may therefore play a role in determining the rate of escape from CTL responses in vivo. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |