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Related Experiment Videos

Human immunodeficiency viruses: neutralization and receptors.

R A Weiss1, P R Clapham, M O McClure

  • 1Institute of Cancer Research, Chester Beatty Laboratories, London, U.K.

Journal of Acquired Immune Deficiency Syndromes
|January 1, 1988
PubMed
Summary

Neutralizing antibodies target HIV envelope glycoproteins gp120 and gp41. The CD4 receptor is crucial for HIV entry into T-lymphocytes and monocytes, but not essential for glial or muscle cell infection.

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Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Human immunodeficiency virus (HIV) envelope glycoproteins, gp120 and gp41, possess epitopes targeted by neutralizing antibodies.
  • Group-specific neutralization antigens common to most HIV-1 isolates exist, with some HIV-2 antisera cross-neutralizing HIV-1.
  • Neutralization epitopes on HIV-1 gp41 (group-specific) and gp120 (type-specific) have been identified and mapped.

Purpose of the Study:

  • To investigate the role of CD4 as a receptor for HIV.
  • To characterize the binding interaction between HIV gp120 and the CD4 receptor.
  • To assess the necessity of CD4 for HIV infection in different cell types.

Main Methods:

  • Analysis of human sera from HIV-infected individuals.

Related Experiment Videos

  • In vitro selection of neutralization escape mutants using monoclonal antibodies (mAbs).
  • Binding assays using CD4 antigen and HIV-1 gp120.
  • Experiments with anti-idiotypic sera against CD4 mAbs and soluble recombinant CD4 (sCD4).
  • Assessment of HIV plating on glial and muscle tumor cells with and without anti-CD4 mAbs or sCD4.
  • Main Results:

    • The CD4 antigen binds HIV-1 gp120 with high affinity, serving as the receptor for HIV-1, HIV-2, and SIV on T-lymphocytes and monocytes.
    • HIV internalization occurs via a pH-independent process following CD4 binding, with the N-terminal V domain of CD4 being the primary binding site for gp120.
    • Anti-idiotypic sera to CD4 mAbs and sCD4 demonstrated neutralization capabilities against various HIV strains, while neither inhibited HIV plating on glial or muscle cells.

    Conclusions:

    • CD4 is essential for HIV entry into T-lymphocytes and monocytes, mediating high-affinity binding and subsequent internalization.
    • The CD4-gp120 interaction is a key target for therapeutic neutralization strategies.
    • CD4 is not indispensable for HIV infection of certain non-lymphoid cell types, such as glial and muscle cells.