Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals.
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.
2.Division of Experimental Medicine, 1001 Potrero Ave., Bldg. 3, Room 603, Box 1234, San Francisco, CA 94110, USA. douglas.nixon@ucsf.edu.
Rui André Saraiva
RA
Raposo
Mohamed
M
Abdel-Mohsen
Sara J
SJ
Holditch
Peter J
PJ
Kuebler
Rex G
RG
Cheng
Emily M
EM
Eriksson
Wilson
W
Liao
Satish K
SK
Pillai
Douglas F
DF
Nixon
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003564:Cytidine Deaminase / Q000502:physiology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics*; D015797:HLA-B35 Antigen / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology; D011506:Proteins / Q000502:physiology; D019713:Receptors, CCR5 / Q000502:physiology; D015728:Receptors, HIV / Q000032:analysis; D000076106:SAM Domain and HD Domain-Containing Protein 1
C584933:CCR5 protein, human; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; C103707:HLA-B57 antigen; D011506:Proteins; D019713:Receptors, CCR5; D015728:Receptors, HIV; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase; D020559:Monomeric GTP-Binding Proteins
HIV-1; HLA class I; restriction factors