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Related Experiment Videos

Constitutive cell surface association between CD4 and CCR5.

X Xiao1, L Wu, T S Stantchev

  • 1Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Miller Drive, Frederick, MD 21702-1201, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 23, 1999
PubMed
Summary

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The human immunodeficiency virus type 1 (HIV-1) receptor CD4 directly binds to the coreceptor CCR5 before viral entry. This interaction, independent of viral proteins, suggests new therapeutic targets for HIV-1 infection and vaccine development.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) entry requires interaction between the viral envelope glycoprotein (Env), CD4 receptor, and a coreceptor, typically CCR5.
  • Understanding the initial molecular interactions is crucial for developing effective antiviral strategies.

Purpose of the Study:

  • To investigate the direct association between CD4 and coreceptors in the absence of viral ligands.
  • To explore the potential role of this interaction in HIV-1 entry and pathogenesis.

Main Methods:

  • Coimmunoprecipitation assays were used to detect the association between CD4 and CCR5/CXCR4.
  • Antibody inhibition assays were performed to assess the functional relevance of the CD4-CCR5 interaction.

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Main Results:

  • CD4 specifically associates with CCR5 constitutively, independent of HIV-1 gp120.
  • This CD4-CCR5 interaction is significantly stronger than CD4-CXCR4 association and is not enhanced by gp120.
  • Antibodies targeting CD4 or CCR5 inhibited this interaction and HIV-1 infection.

Conclusions:

  • A direct, constitutive interaction exists between CD4 and CCR5, likely mediated by specific domains of each protein.
  • This interaction may play a role in HIV-1 entry and pathogenesis, offering potential new targets for antiretroviral drugs and vaccine development.
  • The constitutive association of G protein-coupled receptors highlights novel possibilities for receptor cross-talk.