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

Oren J. Cohen, Mauro Vaccarezza, Gordon K. Lam, Barbara F. Baird, Kathryn Wildt, Philip M. Murphy, Peter A. Zimmerman, Thomas B. Nutman, Cecil H. Fox, Shelley Hoover, Joseph Adelsberger, Michael Baseler, James Arthos, Richard T. Davey, Robin L. Dewar, Julia Metcalf, Douglas J. Schwartzentruber, Jan M. Orenstein, Susan Buchbinder, Alfred J. SaahRoger Detels, John Phair, Charles Rinaldo, Joseph Bernard Margolick, Giuseppe Pantaleo, Anthony S. Fauci

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1581-1589
Number of pages9
JournalJournal of Clinical Investigation
Volume100
Issue number6
Publication statusPublished - Sep 15 1997

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Keywords

  • CC chemokine receptor 5
  • Disease progression
  • HIV-1
  • Lymph nodes
  • Polymorphism

ASJC Scopus subject areas

  • Medicine(all)

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