title: HIV-2 genomic RNA accumulates in stress granules in the absence of active translation.
abstract: During the post-transcriptional events of the HIV-2 replication cycle, the full-length unspliced genomic RNA (gRNA) is first used as an mRNA to synthesize Gag and Gag-Pol proteins and then packaged into progeny virions. However, the mechanisms responsible for the coordinate usage of the gRNA during these two mutually exclusive events are poorly understood. Here, we present evidence showing that HIV-2 expression induces stress granule assembly in cultured cells. This contrasts with HIV-1, which interferes with stress granules assembly even upon induced cellular stress. Moreover, we observed that the RNA-binding protein and stress granules assembly factor TIAR associates with the gRNA to form a TIAR-HIV-2 ribonucleoprotein (TH2RNP) complex localizing diffuse in the cytoplasm or aggregated in stress granules. Although the assembly of TH2RNP in stress granules did not require the binding of the Gag protein to the gRNA, we observed that increased levels of Gag promoted both translational arrest and stress granule assembly. Moreover, HIV-2 Gag also localizes to stress granules in the absence of a 'packageable' gRNA. Our results indicate that the HIV-2 gRNA is compartmentalized in stress granules in the absence of active translation prior to being selected for packaging by the Gag polyprotein.
authors.affiliation: Programa de Virología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 8389100, Santiago, Chile rsotorifo@med.uchile.cl.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Soto-Rifo
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, H3T 1E2, Canada Department of Medicine, Division of Experimental Medicine and Department of Microbiology & Immunology, McGill University, Montréal, Quebec, H3A 2B4, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Valiente-Echeverria
authors.affiliation: INSERM U1111, CIRI, Lyon, F-69364, France Ecole Normale Supérieure de Lyon, Lyon, F-69364, France.
authors.forename: Paulina S
authors.initials: PS
authors.lastname: Rubilar
authors.affiliation: Programa de Virología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 8389100, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-de-Gracia
authors.affiliation: INSERM U1111, CIRI, Lyon, F-69364, France Ecole Normale Supérieure de Lyon, Lyon, F-69364, France.
authors.forename: Emiliano P
authors.initials: EP
authors.lastname: Ricci
authors.affiliation: INSERM U1111, CIRI, Lyon, F-69364, France Ecole Normale Supérieure de Lyon, Lyon, F-69364, France.
authors.forename: Taran
authors.initials: T
authors.lastname: Limousin
authors.affiliation: INSERM U1111, CIRI, Lyon, F-69364, France Ecole Normale Supérieure de Lyon, Lyon, F-69364, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Décimo
authors.affiliation: HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, H3T 1E2, Canada Department of Medicine, Division of Experimental Medicine and Department of Microbiology & Immunology, McGill University, Montréal, Quebec, H3A 2B4, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
authors.affiliation: INSERM U1111, CIRI, Lyon, F-69364, France Ecole Normale Supérieure de Lyon, Lyon, F-69364, France rsotorifo@med.uchile.cl.
authors.forename: Théophile
authors.initials: T
authors.lastname: Ohlmann
mesh_terms: D003594:Cytoplasmic Granules / Q000378:metabolism / Q000821:virology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D016679:Genome, Viral; D015498:HIV-2 / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D013312:Stress, Physiological; D019065:Virus Assembly; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015852:Eukaryotic Initiation Factor-2; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C076751:TIAL1 protein, human