Infection with “Escaped ” Virus Variants Impairs Control of Simian Immunodeficiency Virus SIVmac239 Replication in

An understanding of the mechanism(s) by which some individuals spontaneously control human immuno-deficiency virus (HIV)/simian immunodeficiency virus replication may aid vaccine design. Approximately 50% of Indian rhesus macaques that express the major histocompatibility complex (MHC) class I alleleMamu-B*08 become elite controllers after infection with simian immunodeficiency virus SIVmac239. Mamu-B*08 has a binding motif that is very similar to that of HLA-B27, a human MHC class I allele associated with the elite control of HIV, suggesting that SIVmac239-infected Mamu-B*08-positive (Mamu-B*08) animals may be a good model for the elite control of HIV. The association with MHC class I alleles implicates CD8 T cells and/or natural killer cells in the control of viral replication. We therefore introduced point mutations into eight Mamu-B*08-restricted CD8 T-cell epitopes to investigate the contribution of epitope-specific CD8 T-cell responses to the development of the control of viral replication. TenMamu-B*08macaques were infected with this mutant virus, 8X-SIVmac239. We compared immune responses and viral loads of these animals to those of wild-type SIVmac239-infected Mamu-B*08 macaques. The five most immunodominant Mamu-B*08-re