Several studies consistently associate HLA-B*27 and HLA-B*57 with low set-point viremia and long-term nonprogressive, chronic HIV-1 infection. The study of HLA class I alleles in the context of HIV-1 is well-documented and has led to the discovery of major genetic determinants linked to disease progression and viral control. Our results provide insights into natural protection mechanisms and immunity against HIV-1 that fall outside of classical HLA-mediated effects. To our knowledge, this is the first report showing distinct associations between host restriction factors and HLA class I genotype. We detected significant correlations between CD4 + T cell activation and expression of several APOBEC3 family members, BST-2/tetherin, SAMHD1, and TRIM5α in HLA-B*57-positive individuals. Interestingly, HLA-B*57 individuals have significantly lower CD4 + T cell frequencies but harbor slightly more activated CD4 + T cells compared with their HLA-B*35 counterparts. Our results demonstrate that healthy, uninfected HLA-B*57-positive individuals exhibit significantly higher gene-expression levels of host restriction factors, such as APOBEC3A, APOBEC3B, BST-2/tetherin, and ISG15. In this report, we investigated the association between host restriction factors, other established immunological parameters, and HLA type in HIV-1-seronegative individuals. However, there is considerable heterogeneity in HIV-1 disease progression rates among HLA-B*57-positive subjects, suggesting that additional factors may help to contain viral replication. The HLA-B*57 allele is strongly associated with viremic suppression and slower disease progression. The genetic background of HIV-1-infected subjects, particularly the HLA class I haplotype, appears to be critical in determining disease progression rates, thought to be a result of the role of HIV-1-specific CD8 + T cell responses. We detected significant correlations between CD4(+) T cell activation and expression of several APOBEC3 family members, BST-2/tetherin, SAMHD1, and TRIM5α in HLA-B*57-positive individuals. Interestingly, HLA-B*57 individuals have significantly lower CD4(+) T cell frequencies but harbor slightly more activated CD4(+) T cells compared with their HLA-B*35 counterparts. The genetic background of HIV-1-infected subjects, particularly the HLA class I haplotype, appears to be critical in determining disease progression rates, thought to be a result of the role of HIV-1-specific CD8(+) T cell responses.
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