Infection with “Escaped” Virus Variants Impairs Control of Simian Immunodeficiency Virus SIVmac239 Replication inMamu-B*08-Positive Macaques

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Abstract
An understanding of the mechanism(s) by which some individuals spontaneously control human immunodeficiency 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*08become 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-infectedMamu-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*08+macaques were infected with this mutant virus, 8X-SIVmac239. We compared immune responses and viral loads of these animals to those of wild-type SIVmac239-infectedMamu-B*08+macaques. The five most immunodominant Mamu-B*08-restricted CD8+T-cell responses were barely detectable in 8X-SIVmac239-infected animals. By 48 weeks postinfection, 2 of 10 8X-SIVmac239-infectedMamu-B*08+animals controlled viral replication to Mamu-B*08+animals had viral loads of P= 0.04). Our results suggest that these epitope-specific CD8+T-cell responses may play a role in establishing the control of viral replication inMamu-B*08+macaques.