Publication:

The human immunodeficiency virus type 1 regulatory protein Tat inhibits interferon-induced iNos activity in a murine macrophage cell line (1996)

Author(s): C. H. Barton;T. E. Biggs;T. R. Mee;D. A. Mann

  • : The human immunodeficiency virus type 1 regulatory protein Tat inhibits interferon-induced iNos activity in a murine macrophage cell line

Abstract: Human immunodeficiency virus type 1 (HIV-1) infection is frequently associated with concurrent infection by opportunistic pathogens, against which production of nitric oxide by host macrophages provides a first line of defence. We have investigated whether regulatory HIV-1 proteins, such as Tat, can modulate the activity of the inducible nitric oxide synthase (iNos) gene when expressed in stable transfectant lines of RAW264.7 cells. A bioassay for Tat, based on transactivation of an HIV-1 LTR-CAT reporter gene, allowed selection of Tat-expressing cells. Parental and Tat-expressing macrophages accumulated identical levels of nitrite following lipopolysaccharide (LPS) stimulation. Interferon gamma (IFN-gamma) stimulation however, resulted in reduced levels of nitrite accumulation as a direct consequence of Tat expression. Conditioned media from Tat-expressing cells reduced the level of nitrite accumulation in parental cells following IFN-gamma stimulation but not stimulation with LPS. These results implicate HIV-1 Tat as a modulator of the IFN-gamma-specific signal transduction pathways leading to iNos expression.

Notes: 0022-1317 (Print) Journal Article

  • Short Title: The human immunodeficiency virus type 1 regulatory protein Tat inhibits interferon-induced iNos activity in a murine macrophage cell line
  • Date: Aug
  • Journal: J Gen Virol
  • Volume: 77 ( Pt 8)
  • Pages: 1643-7
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Animals Cell Line Gene Expression Regulation, Viral Gene Products, tat/genetics/*physiology HIV-1/*physiology Humans Interferon Type II/pharmacology Macrophages/cytology/*metabolism Mice Nitric Oxide Synthase/*genetics Nitrites/metabolism Research Support, Non-U.S. Gov't Transfection

Staff

Professor Derek Mann
Prof of Hepatology