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Interferon-gamma inhibits HIV-induced invasiveness of monocytes

S Dhawan1, L M Wahl, A Heredia

  • 1Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852-1448, USA.

Journal of Leukocyte Biology
|December 1, 1995
PubMed

Insights

Interferon-gamma reduces HIV-infected monocyte invasiveness and matrix metalloproteinase-9 (MMP-9) secretion. This suggests a potential therapeutic strategy for controlling HIV pathogenesis by targeting monocyte activity.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human immunodeficiency virus (HIV)-infected monocytes exhibit increased invasiveness.
  • These cells secrete high levels of matrix metalloproteinase-9 (MMP-9), an enzyme crucial for basement membrane degradation.

Purpose of the Study:

  • To investigate the effect of interferon-gamma (IFN-γ) on the invasiveness and MMP-9 production of HIV-infected monocytes.
  • To elucidate the mechanism by which IFN-γ influences monocyte behavior during HIV infection.

Main Methods:

  • Utilized matrigel as a model basement membrane to assess monocyte invasiveness.
  • Treated monocytes with IFN-γ at different time points relative to HIV infection.
  • Quantified MMP-9 levels and assessed HIV integration and replication.

Main Results:

  • IFN-γ treatment significantly inhibited the invasiveness of HIV-infected monocytes.
  • IFN-γ reduced MMP-9 secretion by HIV-infected monocytes, independent of antiviral activity.
  • Monocyte invasiveness and MMP-9 production required active HIV infection, not just viral components.

Conclusions:

  • IFN-γ down-regulates MMP-9 levels and reduces invasiveness in HIV-infected monocytes.
  • This effect appears to be independent of IFN-γ's direct antiviral activity.
  • Targeting MMP-9 via IFN-γ may be a viable strategy for controlling HIV pathogenesis.

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