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Determination of HIV-1 Chemokine Coreceptor Tropism Using Transduced Human Osteosarcoma (HOS) Cells

  • Mark K. Louder
  • John R. Mascola
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 17)

Abstract

CD4 was identified in 1984 as the receptor for HIV-1 (1,2). However, it was soon apparent that a second receptor was necessary for HIV-1 infection of CD4+ cells. This coreceptor was first identified by Berger and colleagues who showed that fusion and entry of T-cell line-adapted strains of HIV-1 into CD4+ cells were mediated by a member of the seven transmembrane chemokine receptor family (3). This protein was initially termed “fusin” and later found to be the α-chemokine receptor CXCR4. Subsequent reports by several laboratories rapidly identified a β-chemokine receptor, CCR5, that mediated entry of macrophage tropic HIV-1 isolates into CD4+ cells (4, 5, 6, 7, 8). Since these initial reports, our understanding of HIV-1 cell entry has continued to evolve. It now seems clear that primary HIV-1 strains with a nonsyncytium-inducing pheno-type (in MT2 cells) utilize the CCR5 coreceptor and are designated “R5,” whereas syncytium-inducing viruses preferentially utilize CXCR4, but may be dual tropic and are designated either “X4” or X4R5, respectively (9,10). Some viruses also appear to be able to utilize chemokine receptors CCR2B and CCR3 (7, 8, 9, 10). In addition, the role of chemokine coreceptors in the pathophysiology of HIV-1 infection and disease progression is just beginning to be understood. Individuals who are homozygous for a 32-bp deletion in the CCR5 gene are only rarely found to be HIV-1-infected, and the heterozygous CCR5/Δccr5 genotype has been associated with a survival advantage against HIV-1 disease progression (11, 12, 13, 14).

Keywords

CCR5 Gene Reference Reagent Program CCR5 Coreceptor Entire Surface Area Coreceptor Tropism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Humana Press Inc., Totowa, NJ 1999

Authors and Affiliations

  • Mark K. Louder
    • 1
  • John R. Mascola
    • 2
  1. 1.Henry M. Jackson FoundationRockville
  2. 2.Division of RetrovirologyWalter Reed Army Institute of ResearchRockville

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