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

American Association for the Advancement of Science (AAAS) - Tập 273 Số 5283 - Trang 1856-1862 - 1996
Michael Dean1, Mary Carrington2, Cheryl A. Winkler2, Gavin Huttley1, Michael W. Smith2, Rando Allikmets1, James J. Goedert3, Susan Buchbinder4, Eric Vittinghoff4, Edward D. Gomperts5, Sharyne Donfield6, David Vlahov7, Richard A. Kaslow8, Alfred J. Saah9, Charles R. Rinaldo10, Roger Detels11, Stephen J. O’Brien1
1M. Dean, G. A. Huttley, R. Allikmets, S. J. O'Brien, Laboratory of Genomic Diversity, National Cancer Institute (NCI), Frederick, MD 21702-1201, USA.
2M. Carrington, C. Winkler, M. W. Smith, Intramural Research Support Program, Science Applications International Corporation Frederick, NCI, Frederick, MD 21702-1201, USA.
3J. J. Goedert, Viral Epidemiology Branch, NCI-Executive Plaza North, 6130 Executive Boulevard, Bethesda, MD 20892, USA.
4S. P. Buchbinder and E. Vittinghoff, San Francisco City Clinic, Department of Public Health, 24 Van Ness Avenue, San Francisco, CA 94102-8033, USA.
5E. Gomperts, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.
6S. Donfield, New England Research Institute, Incorporated, 9 Galen Street, Watertown, MA 02172, USA.
7D. Vlahov, Department of Epidemiology, The Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
8R. Kaslow, Department of Epidemiology, University of Alabama at Birmingham, 720 South 20th Street, Birmingham, AL 35294-0008, USA.
9A. Saah, The Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
10C. Rinaldo, University of Pittsburgh School of Public Health, 4200 5th Avenue, Pittsburgh, PA 15213, USA.
11R. Detels, University of California, Los Angeles, Schools of Public Health and Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90025-1772, USA.

Tóm tắt

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.

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American Association for the Advancement of Science (AAAS)

Tập 273 Số 5283

1856-1862

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