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Antagonistic effect of interferon-gamma on tat-induced transactivation of HIV long terminal repeat

D Emilie1, M C Maillot, J F Nicolas

  • 1Institut National de la Santé et de la Recherche Médicale, Clamart, France.

The Journal of Biological Chemistry
|October 15, 1992
PubMed

Insights

Interferon-gamma (IFN-gamma) inhibits human immunodeficiency virus (HIV) replication by blocking viral gene transactivation. This immune signaling molecule antagonizes the tat protein

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Interferon-gamma (IFN-gamma) is known to inhibit human immunodeficiency virus (HIV) replication in macrophages.
  • The precise mechanism and stage of the HIV infectious cycle affected by IFN-gamma remain unclear.

Purpose of the Study:

  • To investigate the specific site of action of IFN-gamma on the HIV infectious cycle.
  • To determine if IFN-gamma affects the transactivation of the HIV long terminal repeat (LTR) and its interaction with the tat protein.

Main Methods:

  • Utilized the HT4LacZ-1 indicator cell line, a CD4+ HeLa cell line containing an HIV LTR-LacZ gene.
  • Employed a computer-assisted image analyzer to quantify transactivated foci, transactivation levels, and cell fusion potency after HIV infection.
  • Assessed IFN-gamma's effect on tat-induced LTR transactivation using tat expression vectors and cell fusion techniques.

Main Results:

  • IFN-gamma significantly reduced the number of transactivated foci by 75% in HIV-infected HT4LacZ-1 cells.
  • The remaining foci showed reduced transactivation levels, and infected cell fusion potency was decreased.
  • IFN-gamma's inhibitory effect occurred post-HIV entry and was independent of reverse transcription.
  • IFN-gamma antagonized tat-induced LTR transactivation, even when tat was supplied exogenously.

Conclusions:

  • IFN-gamma inhibits HIV replication by interfering with tat-mediated LTR transactivation, likely by affecting cellular factors interacting with tat.
  • These findings suggest a role for IFN-gamma in the establishment of HIV latency, particularly given its elevated levels during HIV infection.

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