HIV evolution: CTL escape mutation and reversion after transmission |
| |
Authors: | Leslie A J Pfafferott K J Chetty P Draenert R Addo M M Feeney M Tang Y Holmes E C Allen T Prado J G Altfeld M Brander C Dixon C Ramduth D Jeena P Thomas S A St John A Roach T A Kupfer B Luzzi G Edwards A Taylor G Lyall H Tudor-Williams G Novelli V Martinez-Picado J Kiepiela P Walker B D Goulder P J R |
| |
Institution: | Department of Pediatrics, Fuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK. |
| |
Abstract: | Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|