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Related Experiment Videos

Structure-function studies of the HIV-1 coreceptors

J F Berson1, R W Doms

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania, 806A Abramson, 34th St. and Civic Center Blvd, Philadelphia, PA, 19104, USA.

Seminars in Immunology
|July 7, 1998
PubMed
Summary

Understanding how G protein-coupled receptors facilitate HIV entry is crucial. These studies reveal distinct structural requirements for coreceptor activity and how HIV entry mechanisms evolve.

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Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Ten seven-transmembrane-domain G protein-coupled receptors (GPCRs) function as coreceptors for HIV-1, HIV-2, and SIV.
  • The specific structural features enabling these GPCRs to mediate viral entry remain largely unknown.

Purpose of the Study:

  • To elucidate the structural determinants of GPCR coreceptor activity in HIV and related virus entry.
  • To investigate the mechanisms of viral entry inhibition by small molecules and chemokines.
  • To hypothesize the evolution of coreceptor utilization during infection.

Main Methods:

  • Structure-function analyses of GPCRs and viral envelope proteins.
  • Assays to determine G protein coupling and receptor internalization requirements for viral fusion.

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  • Studies on the inhibition of viral entry by small molecules and chemokines.

    • Main Results:

    • Coreceptor activity determinants are distinct for each GPCR.
    • Viral entry depends on multiple extracellular domains of GPCRs.
    • Different viral envelope proteins interact uniquely with the same GPCR.
    • G protein coupling and receptor internalization are not essential for viral fusion in cell lines.
    • Small molecule inhibitors of HIV entry mechanisms were identified.
    • A hypothesis for the evolution of coreceptor usage during infection was proposed.

    Conclusions:

    • GPCR structure-function relationships are complex and virus-specific.
    • Viral entry and inhibition mechanisms involve multiple molecular interactions.
    • Understanding these interactions provides insights into viral evolution and therapeutic strategies.