Increased expression of intrinsic antiviral genes in HLA-B57-positive individuals

• Published in: Journal of leukocyte biology Vol. 94; no. 5; pp. 1051 - 1059
• Main Authors: Raposo, Rui André Saraiva, Abdel‐Mohsen, Mohamed, Holditch, Sara J., Kuebler, Peter J., Cheng, Rex G., Eriksson, Emily M., Liao, Wilson, Pillai, Satish K., Nixon, Douglas F.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.11.2013
• Subjects: Acquired Immunodeficiency Syndrome - immunology; CD4-Positive T-Lymphocytes - immunology; Cytidine Deaminase - physiology; Female; HIV-1 - immunology; HIV‐1; HLA class I; HLA-B Antigens - genetics; HLA-B35 Antigen - genetics; Human immunodeficiency virus 1; Humans; Lymphocyte Activation; Male; Middle Aged; Monomeric GTP-Binding Proteins - physiology; Proteins - physiology; Receptors, CCR5 - physiology; Receptors, HIV - analysis; restriction factors; SAM Domain and HD Domain-Containing Protein 1; Translational & Clinical Immunology; HIV-1; HLA class I; restriction factors
• ISSN: 0741-5400; 1938-3673; 1938-3673
• DOI: 10.1189/jlb.0313150

Novel association between intrinsic viral resistance genes and HLA class I provide additional mechanistic determinants in HIV‐1 disease outcomes. 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. The HLA‐B*57 allele is strongly associated with viremic suppression and slower disease progression. 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. In this report, we investigated the association between host restriction factors, other established immunological parameters, and HLA type in HIV‐1‐seronegative individuals. 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. 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. 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. To our knowledge, this is the first report showing distinct associations between host restriction factors and HLA class I genotype. Our results provide insights into natural protection mechanisms and immunity against HIV‐1 that fall outside of classical HLA‐mediated effects.