title: Activation of GCN2 upon HIV-1 infection and inhibition of translation.
abstract: Higher eukaryotic organisms have a variety of specific and nonspecific defense mechanisms against viral invaders. In animal cells, viral replication may be limited through the decrease in translation. Some viruses, however, have evolved mechanisms that counteract the response of the host. We report that infection by HIV-1 triggers acute decrease in translation. The human protein kinase GCN2 (eIF2AK4) is activated by phosphorylation upon HIV-1 infection in the hours following infection. Thus, infection by HIV-1 constitutes a stress that leads to the activation of GCN2 with a resulting decrease in protein synthesis. We have shown that GCN2 interacts with HIV-1 integrase (IN). Transfection of IN in amino acid-starved cells, where GCN2 is activated, increases the protein synthesis level. These results point to an as yet unknown role of GCN2 as an early mediator in the cellular response to HIV-1 infection, and suggest that the virus is able to overcome the involvement of GCN2 in the cellular response by eliciting methods to maintain protein synthesis.
authors: UMR 5234 CNRS, Université Bordeaux Segalen, 146 Rue Léo Saignat, 33076 Bordeaux cedex, France.
authors: Ophélie
authors: O
authors: Cosnefroy
authors: Anaïs
authors: A
authors: Jaspart
authors: Christina
authors: C
authors: Calmels
authors: Vincent
authors: V
authors: Parissi
authors: Hervé
authors: H
authors: Fleury
authors: Michel
authors: M
authors: Ventura
authors: Sandrine
authors: S
authors: Reigadas
authors: Marie-Line
authors: ML
authors: Andréola
mesh_terms: D020868:Gene Silencing; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D019427:HIV Integrase / Q000378:metabolism / Q000502:physiology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D014779:Virus Replication
chemical_list: C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1