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Fusion from without directed by human immunodeficiency virus particles

F Clavel1, P Charneau

  • 1Département SIDA et Rétrovirus, Institut Pasteur, Paris, France.

Journal of Virology
|February 1, 1994
PubMed
Summary

Human immunodeficiency virus (HIV) particles can cause cell fusion without replicating. This "fusion from without" mechanism, even with defective HIV, contributes to HIV infection

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Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Enveloped viruses can induce cell fusion independent of viral replication, a process termed "fusion from without."
  • Human immunodeficiency virus (HIV) infection is characterized by CD4 cell depletion, a key factor in disease progression.

Purpose of the Study:

  • To investigate whether human immunodeficiency virus (HIV) particles can mediate "fusion from without."
  • To explore the implications of this mechanism in HIV pathogenesis.

Main Methods:

  • Utilized HeLa-CD4 cells with a Tat-inducible lacZ reporter gene to detect syncytia formation.
  • Exposed cells to HIV particles, including replication-defective integrase mutants, with and without zidovudine treatment.
  • Assessed fusion inhibition using V3 loop-specific monoclonal antibodies and soluble CD4.

Main Results:

  • HIV particles efficiently induced syncytia formation in HeLa-CD4 cells within 6 hours, preceding detectable viral gene expression.
  • Zidovudine treatment inhibited HIV replication and expression but not cell-cell fusion.
  • Fusion was mediated by replication-defective HIV integrase mutant particles.
  • Monoclonal antibodies targeting the V3 loop and soluble CD4 blocked HIV-induced fusion.

Conclusions:

  • HIV particles can induce "fusion from without," a mechanism independent of viral replication.
  • This fusion process can be mediated by replication-defective HIV particles.
  • The "fusion from without" mechanism may contribute to the CD4 cell depletion observed in HIV infection.

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