HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase

J Interferon Cytokine Res. 1997 Aug;17(8):461-7. doi: 10.1089/jir.1997.17.461.

Abstract

The p17 matrix protein of the human immunodeficiency virus type 1 (HIV-1) plays a crucial role in AIDS pathogenesis. It orchestrates viral assembly and directs the preintegration complex to the nucleus of infected cells. Recently, the three-dimensional structure of p17 was shown to resemble that of interferon-gamma (IFN-gamma), suggesting that both proteins might share analogous functions. We demonstrate that in monocytes, p17 shares with IFN-gamma the ability to induce 1alpha-hydroxylase activity and to activate fructose 1,6-bisphosphatase gene expression in the presence of 25-hydroxyvitamin D3. However, p17 does not bind to the IFN-gamma cell membrane receptor and fails to increase expression of IFN-gamma-induced proteins, such as tryptophanyl-tRNA synthetase, Fc gammaRI, and HLA DR or B7/BB1 antigens. Altogether, our results raise the possibility that the structural resemblance between p17 and IFN-gamma causes the selective activation of a common pathway resulting in the production of 1,25-dihydroxyvitamin D3. We also found that unlike IFN-gamma, p17 increases the intracellular ATP content. Since transport of the HIV-1 preintegration complex through the nuclear membrane is an ATP-dependent process, our observation suggests that p17 plays a double role in this active transport, not only by acting as a chaperone molecule but also by recruiting the necessary energy for this process.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / biosynthesis
  • Calcifediol / pharmacology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Drug Synergism
  • Enzyme Induction
  • Fructose-Bisphosphatase / biosynthesis*
  • Gene Expression Regulation / drug effects
  • Gene Products, gag / pharmacology*
  • HIV Antigens / pharmacology*
  • Humans
  • Interferon Inducers
  • Interferon-gamma / pharmacology*
  • Ligands
  • Monocytes / metabolism
  • Peptide Fragments / metabolism
  • Receptors, Interferon / chemistry
  • Receptors, Interferon / metabolism
  • Recombinant Proteins
  • Viral Proteins*
  • gag Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, gag
  • HIV Antigens
  • Interferon Inducers
  • Ligands
  • Peptide Fragments
  • Receptors, Interferon
  • Recombinant Proteins
  • Viral Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1
  • interferon gamma receptor
  • Interferon-gamma
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Fructose-Bisphosphatase
  • Calcifediol