Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the <i>CKR5</i> Structural Gene

• Michael Dean

  M. Dean, G. A. Huttley, R. Allikmets, S. J. O'Brien, Laboratory of Genomic Diversity, National Cancer Institute (NCI), Frederick, MD 21702-1201, USA.

• Mary Carrington

  M. Carrington, C. Winkler, M. W. Smith, Intramural Research Support Program, Science Applications International Corporation Frederick, NCI, Frederick, MD 21702-1201, USA.

• Cheryl Winkler

  M. Carrington, C. Winkler, M. W. Smith, Intramural Research Support Program, Science Applications International Corporation Frederick, NCI, Frederick, MD 21702-1201, USA.

• Gavin A. Huttley

  M. Dean, G. A. Huttley, R. Allikmets, S. J. O'Brien, Laboratory of Genomic Diversity, National Cancer Institute (NCI), Frederick, MD 21702-1201, USA.

• Michael W. Smith

  M. Carrington, C. Winkler, M. W. Smith, Intramural Research Support Program, Science Applications International Corporation Frederick, NCI, Frederick, MD 21702-1201, USA.

• Rando Allikmets

  M. Dean, G. A. Huttley, R. Allikmets, S. J. O'Brien, Laboratory of Genomic Diversity, National Cancer Institute (NCI), Frederick, MD 21702-1201, USA.

• James J. Goedert

  J. J. Goedert, Viral Epidemiology Branch, NCI-Executive Plaza North, 6130 Executive Boulevard, Bethesda, MD 20892, USA.

• Susan P. Buchbinder

  S. P. Buchbinder and E. Vittinghoff, San Francisco City Clinic, Department of Public Health, 24 Van Ness Avenue, San Francisco, CA 94102-8033, USA.

• Eric Vittinghoff

  S. P. Buchbinder and E. Vittinghoff, San Francisco City Clinic, Department of Public Health, 24 Van Ness Avenue, San Francisco, CA 94102-8033, USA.

• Edward Gomperts

  E. Gomperts, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.

• Sharyne Donfield

  S. Donfield, New England Research Institute, Incorporated, 9 Galen Street, Watertown, MA 02172, USA.

• David Vlahov

  D. Vlahov, Department of Epidemiology, The Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.

• Richard Kaslow

  R. Kaslow, Department of Epidemiology, University of Alabama at Birmingham, 720 South 20th Street, Birmingham, AL 35294-0008, USA.

• Alfred Saah

  A. Saah, The Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.

• Charles Rinaldo

  C. Rinaldo, University of Pittsburgh School of Public Health, 4200 5th Avenue, Pittsburgh, PA 15213, USA.

• Roger Detels

  R. Detels, University of California, Los Angeles, Schools of Public Health and Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90025-1772, USA.

• Stephen J. O'Brien

  M. Dean, G. A. Huttley, R. Allikmets, S. J. O'Brien, Laboratory of Genomic Diversity, National Cancer Institute (NCI), Frederick, MD 21702-1201, USA.

抄録

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4 + T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele ( CKR5Δ32 ) was identified that is present at a frequency of ∼0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Δ32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

収録刊行物

• Science

  Science 273 (5283), 1856-1862, 1996-09-27

  American Association for the Advancement of Science (AAAS)

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360011146220474880
• NII論文ID: 80009242629
• DOI: 10.1126/science.273.5283.1856
• ISSN: 10959203
• ISSN: 00368075
• ISSN: http://id.crossref.org/issn/00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.273.5283.1856
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