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CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro

Academic Article
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Overview

authors

  • Salkowitz, J. R.
  • Bruse, S. E.
  • Meyerson, H.
  • Valdez, H.
  • Mosier, Donald
  • Harding, C. V.
  • Zimmerman, P. A.
  • Lederman, M. M.

publication date

  • September 2003

journal

  • Clinical Immunology  Journal

abstract

  • The common CCR5 promoter polymorphism at position -2459 (A/G) has been associated with differences in the rate of progression to AIDS, where HIV-1-infected individuals with the CCR5 -2459 G/G genotype exhibit slower disease progression than those with the A/A genotype. Mechanisms underlying the relationship between these polymorphisms and disease progression are not known. Here through in vitro infection of peripheral blood mononuclear cells obtained from healthy Caucasian blood donors with macrophage-tropic HIV-1 isolates we observed low, medium, and high viral propagation in association with G/G, A/G, and A/A promoter genotypes, respectively. Flow cytometric analysis of unstimulated CD14+ monocytes from these same donors revealed a similar hierarchy of CCR5 receptor density in association with promoter genotypes. Finally, PBMC from persons with the G/G promoter polymorphism produced higher levels of beta-chemokines after in vitro stimulation. Thus, the CCR5 -2459 (A/G) promoter polymorphism determines CCR5 expression and predicts the magnitude of HIV-1 propagation in vitro. These findings may provide important insight regarding the regulation of mechanisms that influence the rate of HIV-1 propagation and progression to AIDS.

subject areas

  • Antigens, CD14
  • Cell Division
  • Cells, Cultured
  • Chemokine CCL4
  • Chemokine CCL5
  • Enzyme-Linked Immunosorbent Assay
  • Genotype
  • HIV Infections
  • HIV-1
  • Humans
  • Macrophage Inflammatory Proteins
  • Macrophages
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Receptors, CCR5
  • Virus Replication
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Identity

PubMed Central ID

  • PMC3728895

International Standard Serial Number (ISSN)

  • 1521-6616

Digital Object Identifier (DOI)

  • 10.1016/s1521-6616(03)00147-5

PubMed ID

  • 14499246
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Additional Document Info

start page

  • 234

end page

  • 240

volume

  • 108

issue

  • 3

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