Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression

Michael W. Smith, Michael Dean, Mary Carrington, Cheryl Winkler, Gavin A. Huttley, Deborah A. Lomb, James J. Goedert, Thomas R. O'Brien, Lisa P. Jacobson, Richard Kaslow, Susan Buchbinder, Eric Vittinghoff, David Vlahov, Keith Hoots, Margaret W. Hilgartner, Stephen J. O'Brien

Research output: Contribution to journalArticle

Abstract

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV- 1 disease progression. A mutation (CCR2-641) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-641 exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-641 allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-641 occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Δ32 (which also delays AIDS onset) and CCR2-641 were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV- 1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for f 6 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Original languageEnglish (US)
Pages (from-to)959-965
Number of pages7
JournalScience
Volume277
Issue number5328
DOIs
StatePublished - Aug 15 1997

ASJC Scopus subject areas

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    Smith, M. W., Dean, M., Carrington, M., Winkler, C., Huttley, G. A., Lomb, D. A., Goedert, J. J., O'Brien, T. R., Jacobson, L. P., Kaslow, R., Buchbinder, S., Vittinghoff, E., Vlahov, D., Hoots, K., Hilgartner, M. W., & O'Brien, S. J. (1997). Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Science, 277(5328), 959-965. https://doi.org/10.1126/science.277.5328.959