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Research Article Free access | 10.1172/JCI119682

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

O J Cohen, M Vaccarezza, G K Lam, B F Baird, K Wildt, P M Murphy, P A Zimmerman, T B Nutman, C H Fox, S Hoover, J Adelsberger, M Baseler, J Arthos, R T Davey Jr, R L Dewar, J Metcalf, D J Schwartzentruber, J M Orenstein, S Buchbinder, A J Saah, R Detels, J Phair, C Rinaldo, J B Margolick, and A S Fauci

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.

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Published September 15, 1997 - More info

Published in Volume 100, Issue 6 on September 15, 1997
J Clin Invest. 1997;100(6):1581–1589. https://doi.org/10.1172/JCI119682.
© 1997 The American Society for Clinical Investigation
Published September 15, 1997 - Version history
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Abstract

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

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