Journal
JOURNAL OF VIROLOGY
Volume 82, Issue 2, Pages 859-870Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01816-07
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Funding
- NATIONAL CANCER INSTITUTE [ZIABC010791] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015459, P51RR000167, C06RR020141, R24RR015371, R24RR016038] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI052056, R01AI049120] Funding Source: NIH RePORTER
- Intramural NIH HHS Funding Source: Medline
- NCI NIH HHS [N01-CO-12400, N01CO12400] Funding Source: Medline
- NCRR NIH HHS [P51 RR000167, C06 RR015459, C06 RR020141, RR15459-01, R24-RR015371, R24-RR016038, RR020141-01, R24 RR016038, R24 RR015371, P51-RR000167] Funding Source: Medline
- NIAID NIH HHS [R01-AI052056, R01-AI049120, R01 AI052056, R01 AI049120] Funding Source: Medline
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The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4' T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-11 allelles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of < 0.0001). The study of MHC-II allelles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.
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