HIV evolution: CTL escape mutation and reversion after transmission.
Leslie AJ., Pfafferott KJ., Chetty P., Draenert R., Addo MM., Feeney M., Tang Y., Holmes EC., Allen T., Prado JG., Altfeld M., Brander C., Dixon C., Ramduth D., Jeena P., Thomas SA., St John A., Roach TA., Kupfer B., Luzzi G., Edwards A., Taylor G., Lyall H., Tudor-Williams G., Novelli V., Martinez-Picado J., Kiepiela P., Walker BD., Goulder PJ.
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.