Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity.

Abstract

Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA-B alleles can be divided into two mutually exclusive groups based on the expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to its role in presenting viral peptides for immune recognition, the HLA-Bw4, but not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is significantly associated with homozygosity for HLA-B alleles that share the HLA-Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly associated with the ability to remain AIDS free and to maintain a normal CD4 T cell count in a second cohort of HIV-1-infected individuals with well defined dates of seroconversion. This association was independent of the presence of a mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1 infection, and it was independent of the presence of HLA alleles that could potentially confound the results. We conclude that homozygosity for HLA-Bw4-bearing B alleles is associated with a significant advantage and that the HLA-Bw4 motif is important in AIDS pathogenesis.

• Authors: P O Flores-Villanueva, E J Yunis, J C Delgado, E Vittinghoff, S Buchbinder, J Y Leung, A M Uglialoro, O P Clavijo, E S Rosenberg, S A Kalams, J D Braun, S L Boswell, B D Walker, A E Goldfeld
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 98 Issue 9 Pg. 5140-5 (Apr 24 2001) ISSN: 0027-8424 [Print] United States
• PMID: 11309482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes
• HLA-B Antigens
• HLA-Bw4 antigen
• HLA-C Antigens
• Receptors, CCR5
• Receptors, Immunologic
• Receptors, KIR

Topics

• Acquired Immunodeficiency Syndrome (genetics, immunology, virology)
• Adult
• Alleles
• CD4 Lymphocyte Count
• Cohort Studies
• Disease Progression
• Epitopes (immunology)
• Female
• Gene Frequency
• HIV Seropositivity (genetics, immunology, virology)
• HIV-1 (immunology, physiology)
• HLA-B Antigens (genetics, immunology)
• HLA-C Antigens (genetics, immunology)
• Homozygote
• Humans
• Killer Cells, Natural (immunology)
• Male
• Middle Aged
• Mutation (genetics)
• Receptors, CCR5 (genetics)
• Receptors, Immunologic (immunology)
• Receptors, KIR
• Time Factors
• Viral Load
• Viremia (genetics, immunology, virology)