title: Ebola virus VP35 blocks stress granule assembly.
abstract: Stress granules (SGs) are dynamic cytoplasmic aggregates of translationally silenced mRNAs that assemble in response to environmental stress. SGs appear to play an important role in antiviral innate immunity and many viruses have evolved to block or subvert SGs components for their own benefit. Here, we demonstrate that intracellular Ebola virus (EBOV) replication and transcription-competent virus like particles (trVLP) infection does not lead to SG assembly but leads to a blockade to Arsenite-induced SG assembly. Moreover we show that EBOV VP35 represses the assembly of canonical and non-canonical SGs induced by a variety of pharmacological stresses. This SG blockade requires, at least in part, the C-terminal domain of VP35. Furthermore, results from our co-immunoprecipitation studies indicate that VP35 interacts with multiple SG components, including G3BP1, eIF3 and eEF2 through a stress- and RNA-independent mechanism. These data suggest a novel function for EBOV VP35 in the repression of SG assembly.
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2.
authors.forename: Valerie
authors.initials: V
authors.lastname: Le Sage
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2; Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cinti
authors.affiliation: Centre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Toronto, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: McCarthy
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2; Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Raquel
authors.initials: R
authors.lastname: Amorim
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2; Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada H3A 0G4.
authors.forename: Shringar
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554, 09042 Monserrato, Cagliari, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Daino
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554, 09042 Monserrato, Cagliari, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
authors.affiliation: Centre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Toronto, Canada.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Branch
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2; Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4; Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada H3A 0G4. Electronic address: andrew.mouland@mcgill.ca.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000821:virology*; D004265:DNA Helicases; D029043:Ebolavirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D019142:Hemorrhagic Fever, Ebola / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D000072417:Protein Domains; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015852:Eukaryotic Initiation Factor-2; D039621:Eukaryotic Initiation Factor-3; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; C080980:VP35 protein, filovirus; D054334:Viral Regulatory and Accessory Proteins; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: Ebola virus; In vitro GST binding assay; Poliovirus infection; Proximity ligation assay; Stress granule assembly; TIAR recruitment; VP35; trVLP infection