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Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression

Nature Medicine volume 4, pages 786–793 (1998)Cite this article

Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCR5) and CCR2, as well as the ligand for the co-receptor CXCR4, stromal-derived factor (SDF-1), have been associated with a delay in disease progression. We began this study to test whether polymorphisms in the CCRS regulatory regions influence the course of HIV-1 disease, as well as to examine the role of the previously identified allelic variants in 1,090 HIV-1 infected individuals. Here we describe the evolutionary relationships between the phenotypically important CCRS alleles, define precisely the CCR5 regulatory sequences that are linked to the CCR5-Δ32 and CCR2-64I polymorphisms, and identify genotypes associated with altered rates of HIV-1 disease progression. The disease-retarding effects of the CCR2-64I allele were found in African Americans but not in Caucasians, and the SDF1-3′A/3′A genotype was associated with an accelerated progression to death. In contrast, the CCR5-Δ32 allele and a CCR5 promoter mutation with which it is tightly linked were associated with limited disease-retarding effects. Collectively, these findings draw attention to a complex array of genetic determinants in the HIV-host interplay.

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Author notes

  1. Srinivas Mummidi, Seema S. Ahuja and Enrique Gonalez: S.M. S.S.A. & E.G. contributed equally to this work

  2. Sunil K.Ahuja and Matthew J. Dolan: Correspondence should be addressed to S.K.A., e-mail: ahujas@uthscsa.edu or M.J.D., e-mail: dolan@WHMC-LAFB.AF.MIL

Authors and Affiliations

  1. Department of Medicine, University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX, 78284-7870

    Srinivas Mummidi, Seema S. Ahuja, Enrique Gonalez, Elvin N. Santiago, Robert A. Clark & Sunil K. Ahuja

  2. Henry M. Jackson Foundation, Wilford Medical Center, Lackland, AFB, TX, 78236

    Stephanie A. Anderson

  3. Infectious Diseases Service, Department of Medicine, Wilford Hall Medical Center, Lackland AFB, TX, 78236

    Kevin T. Stephan & Matthew J. Dolan

  4. Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78284

    Fiona E. Craig & Peter O'Connell

  5. Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78284

    Victor Tryon

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Mummidi, S., Ahuja, S., Gonalez, E. et al. Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Nat Med 4, 786–793 (1998). https://doi.org/10.1038/nm0798-786

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