HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase.
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.
Besançon
F
F
INSERM Unité 417, Hôpital Saint-Antoine, Paris, France.
Just
J
J
Bourgeade
M F
MF
Van Weyenbergh
J
J
Solomon
D
D
Guillozo
H
H
Wietzerbin
J
J
Cayre
Y E
YE
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D002112:Calcifediol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D004790:Enzyme Induction; D006597:Fructose-Bisphosphatase / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D015683:Gene Products, gag / Q000494:pharmacology*; D015488:HIV Antigens / Q000494:pharmacology*; D006801:Humans; D007369:Interferon Inducers; D007371:Interferon-gamma / Q000494:pharmacology*; D008024:Ligands; D009000:Monocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D017471:Receptors, Interferon / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D000096743:Interferon gamma Receptor
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol; D006597:Fructose-Bisphosphatase; D015683:Gene Products, gag; D015488:HIV Antigens; D007369:Interferon Inducers; D007371:Interferon-gamma; D008024:Ligands; D010446:Peptide Fragments; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D000096743:Interferon gamma Receptor; C054858:p17 protein, Human Immunodeficiency Virus Type 1