Effect of polyanion-resistance on HIV-1 infection

Michael D Bobardt1, Mercedes Armand-Ugón, Imma Clotet

  • 1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Virology
|July 13, 2004
PubMed

Insights

HIV-1 entry inhibitors called polyanions can lead to resistant viruses. A resistant HIV-1 strain shows reduced binding to heparan sulfate proteoglycans (HSPG), limiting its target cell range.

Area of Science:

  • Virology
  • Immunology
  • Biochemistry

Background:

  • Polyanions are effective inhibitors of Human Immunodeficiency Virus type 1 (HIV-1) entry.
  • The emergence of polyanion-resistant HIV-1 strains poses a challenge to therapeutic strategies.
  • Understanding the mechanisms of resistance is crucial for developing new interventions.

Purpose of the Study:

  • To investigate the mechanism by which HIV-1 develops resistance to polyanion inhibitors.
  • To determine the role of heparan sulfate proteoglycans (HSPG) in polyanion-resistant HIV-1 infection.
  • To characterize a novel polyanion-resistant HIV-1 strain for its potential as a research tool.

Main Methods:

  • Comparative analysis of HIV-1 replication in suspension and adherent CD4+ T cells.
  • Assessment of viral binding to cell-surface HSPG.
  • Evaluation of viral infectivity in the presence of polyanions and polycations (polybrene).
  • Mutation analysis of the viral envelope glycoprotein gp120.

Main Results:

  • Polyanion-resistant HIV-1 efficiently replicates in suspension CD4+ T cells but poorly infects adherent CD4+ cells.
  • Mutations associated with polyanion resistance in gp120 lead to decreased binding to HSPG.
  • The polycation polybrene restores HSPG binding and infectivity of the resistant virus in adherent cells.
  • The resistant virus's inability to bind HSPG was confirmed.

Conclusions:

  • Polyanion resistance in HIV-1 is associated with impaired HSPG binding, restricting its cellular tropism.
  • HSPG plays a significant role in mediating HIV-1 infection of adherent cells.
  • This HSPG-binding deficient virus serves as a valuable tool for studying HIV-1-HSPG interactions.
  • Polyanion-resistance mechanisms can modulate HIV-1 pathogenesis by altering target cell accessibility.

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