title: eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection.
abstract: Stress granules (SG) are translationally silent sites of RNA triage induced by environmental stresses including viral infection. Here we show that HIV-1 Gag blocks SG assembly irrespective of eIF2α phosphorylation and even when SG assembly is forced by overexpression of Ras-GAP SH3 domain-binding protein (G3BP1) or TIAR. The overexposed loops in the amino-terminal capsid domain of Gag and host eukaryotic elongation factor 2 (eEF2) are found to be critical for the SG blockade via interaction. Moreover, cyclophilin A (CypA) stabilizes the Gag-eEF2 association. eEF2 depletion not only lifts the SG blockade but also results in impaired virus production and infectivity. Gag also disassembles preformed SGs by recruiting G3BP1, thereby displacing eEF2, revealing another unsuspected virus-host interaction involved in the HIV-1-imposed SG blockade. Understanding how HIV-1 counters anti-viral stress responses will lay the groundwork for new therapeutic strategies to bolster host cell immune defences against HIV-1 and other pathogens.
authors.affiliation: 1] HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2 [2] Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Fernando
authors.initials: F
authors.lastname: Valiente-Echeverría
authors.affiliation: 1] HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2 [2] Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Luca
authors.initials: L
authors.lastname: Melnychuk
authors.affiliation: 1] HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2 [2] Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Kishanda
authors.initials: K
authors.lastname: Vyboh
authors.affiliation: 1] HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2 [2] Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Lara
authors.initials: L
authors.lastname: Ajamian
authors.affiliation: Department of Biochemistry, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Imed-Eddine
authors.initials: IE
authors.lastname: Gallouzi
authors.affiliation: 1] Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4 [2] Research Institute of the McGill University Health Centre, Montréal, Québec, Canada H3H 2R9.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bernard
authors.affiliation: 1] HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2 [2] Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4 [3] Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry*; D002469:Cell Separation; D002522:Chlorocebus aethiops; D002853:Chromatography, Liquid; D004265:DNA Helicases; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D013058:Mass Spectrometry; D051379:Mice; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry; D010802:Phylogeny; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D020365:RNA Helicases; D034622:RNA Interference; D000067776:RNA Recognition Motif Proteins
chemical_list: D002352:Carrier Proteins; D015683:Gene Products, gag; D010455:Peptides; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D049452:Green Fluorescent Proteins; D012313:RNA; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases