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CD8+ T cell-based strong selective pressure on multiple simian immunodeficiency virus targets in macaques possessing a protective MHC class I haplotype

Trang Thi Thu Hau, Midori Nakamura-Hoshi, Yoshiaki Kanno, Takushi Nomura, Masako Nishizawa, Sayuri Seki, Hiroshi Ishii, Ai Kawana-Tachikawa, William W. Hall, Lan Anh Nguyen Thi, Tetsuro Matano, Hiroyuki Yamamoto
Biochemical and biophysical research communications 2019 v.512 no.2 pp. 213-217
CD8-positive T-lymphocytes, Human immunodeficiency virus, Macaca mulatta, Simian immunodeficiency virus, alleles, antigens, haplotypes, major histocompatibility complex, mutation, nucleotide sequences, virus replication
In human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections, host major histocompatibility complex class I (MHC-I) genotypes have a great impact on viral replication and MHC-I-associated viral genome mutations are selected under CD8+ T-cell pressure. Association of MHC-I genotypes with HIV/SIV control has been investigated at MHC-I allele levels but not fully at haplotype levels. We previously established groups of rhesus macaques sharing individual MHC-I haplotypes. In the present study, we compared viral genome diversification after SIV infection in macaques possessing a protective MHC-I haplotype, 90-010-Id, with those possessing a non-protective MHC-I haplotype, 90-010-Ie. These two MHC-I haplotypes are associated with immunodominant CD8+ T-cell responses targeting similar regions of viral Nef antigen. Analyses of viral genome sequences and antigen-specific T-cell responses showed four and two candidates of viral CD8+ T-cell targets associated with 90-010-Id and 90-010-Ie, respectively, in addition to the Nef targets. In these CD8+ T-cell target regions, higher numbers of mutations were detected at the setpoint after SIV infection in macaques possessing 90-010-Id than those possessing 90-010-Ie. These results indicate higher selective pressure on overall CD8+ T-cell targets associated with the protective MHC-I haplotype, suggesting a pattern of HIV/SIV control by multiple target-specific CD8+ T-cell responses.