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 a ssembly and directs the preintegration complex to the nucleus of infec ted 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 mono cytes, p17 shares with IFN-gamma the ability to induce 1 alpha-hydroxy lase activity and to activate fructose 1,6-bisphosphatase gene express ion in the presence of 25-hydroxyvitamin D-3. However, p17 does not bi nd to the IFN-gamma cell membrane receptor and fails to increase expre ssion of IFN-gamma-induced proteins, such as tryptophanyl-tRNA synthet ase, Fc gamma RI, and HLA DR or B7/BB1 antigens, Altogether, our resul ts raise the possibility that the structural resemblance between p17 a nd IFN-gamma causes the selective activation of a common pathway resul ting in the production of 1,25-dihydroxyvitamin D-3. We also found tha t unlike IFN-gamma, p17 increases the intracellular ATP content, Since transport of the HIV-1 preintegration complex through the nuclear mem brane is an ATP-dependent process, our observation suggests that p17 p lays a double role in this active transport, not only by acting as a c haperone molecule but also by recruiting the necessary energy for this process.