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Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
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Stoichiometric parameters of HIV-1 entry.

Melissa Zarr1, Robert Siliciano2

  • 1Johns Hopkins University School of Medicine, 733 N Broadway, Room 872, Baltimore, MD 21205, USA.

Virology
|December 3, 2014
PubMed
Summary

Human immunodeficiency virus type 1 (HIV-1) entry requires few functional spikes, with Env trimers potentially functioning with fewer than three active subunits. Stoichiometric entry requirements for CCR5 and CXCR4 coreceptors are similar.

Keywords:
CCR5CD4CXCR4EntryEnvHIV-2Relative infectivitygp120

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) entry into host cells involves the binding of gp120 trimers to CD4 receptors and either CCR5 or CXCR4 coreceptors.
  • The precise stoichiometric requirements for HIV-1 entry, including the number of gp120 trimers and functional subunits needed, remain poorly understood.

Purpose of the Study:

  • To elucidate the stoichiometric parameters governing HIV-1 entry.
  • To determine the minimum number of gp120 trimers and functional subunits required for viral entry.
  • To compare the stoichiometric requirements for CCR5-mediated versus CXCR4-mediated HIV-1 entry.

Main Methods:

  • Utilized single-round infectivity assays with chimeric HIV-1 viruses.
  • Compared experimental relative infectivity curves with mathematical model-generated curves.
  • Analyzed the functional requirements of Env trimers and their subunits during viral entry.

Main Results:

  • HIV-1 entry can be initiated by a minimal number of functional spikes, specifically one or two.
  • Env trimers can mediate viral entry with fewer than three active gp120 subunits.
  • No significant differences were observed in the stoichiometric requirements for entry mediated by CCR5 or CXCR4 coreceptors.

Conclusions:

  • HIV-1 entry is a highly efficient process requiring a low number of functional Env spikes.
  • The functional plasticity of Env trimers allows for entry with incomplete active subunits.
  • Coreceptor choice (CCR5 vs. CXCR4) does not substantially alter the fundamental stoichiometric needs for HIV-1 entry.