gcn2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infectiongcn2抑制性影响人类免疫缺陷virus-1蛋白质合成和裂解病毒感染.pdfVIP

GCN2 Has Inhibitory Effect on Human Immunodeficiency Virus-1 Protein Synthesis and Is Cleaved upon Viral Infection 1 ´ ´ 2 ´ 1 ´ 1¤ a ´ ˜ ´ 3 Javier del Pino , Jose Luis Jimenez , Ivan Ventoso , Alfredo Castello , M Angeles Munoz-Fernandez , ´ 1 ´ 1 Cesar de Haro , Juan Jose Berlanga * ´ ´ 1 Centro de Biologıa Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain, 2 Plataforma de Laboratorio, Hospital General Universitario ˜ ´ ˜ ´ Gregorio Maranon, Madrid, Spain, 3 Laboratory of Molecular Immunobiology, Hospital General Universitario Gregorio Maranon, Madrid, Spain Abstract The reversible phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2alpha) is a well- characterized mechanism of translational control in response to a wide variety of cellular stresses, including viral infection. Beside PKR, the eIF2alpha kinase GCN2 participates in the cellular response against viral infection by RNA viruses with central nervous system tropism. PKR has also been involved in the antiviral response against HIV-1, although this antiviral effect is very limited due to the distinct mechanisms evolved by the virus to counteract PKR action. Here we report that infection of human cells with HIV-1 conveys the proteolytic cleavage of GCN2 and that purified HIV-1 and HIV-2 proteases produce direct proteolysis of GCN2 in vitro, abrogating the activation of