Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus

Autor: Rincheval, Vincent, Lelek, Mickael, Gault, Elyanne, Bouillier, Camille, Sitterlin, Delphine, Blouquit-Laye, Sabine, Galloux, Marie, Zimmer, Christophe, Eleouet, Jean-François, Rameix-Welti, Marie-Anne
Přispěvatelé: Infection et inflammation chronique (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Imagerie et Modélisation - Imaging and Modeling, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Hôpital Ambroise Paré, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), This study was supported by grants from the ANR (French national research agency), RESPISYNCYCELL project, from the Region Ile-de-France and by the 'Assistance Publique des Hôpitaux de Paris' (AP-HP). M.L and C.Z. acknowledge support from Institut Pasteur and Région Ile de France (DIM Malinf), We thank Dr Qin Yu from AstraZeneca R&D Boston—USA, for providing the AZ27 drug. We are grateful to Felix Rey, Jean-Louis Gaillard, Charles-Adrien Richard and Monica Bajorek for helpful discussions. Benoit Maury is gratefully acknowledged for technical assistance in microscopy experiments. We are grateful to the Cymages platform for access to SP8 Leica, which was supported by grants from the region Ile-de-France. We acknowledge Ignacio Izeddin for the gift of a mEos2 encoding plasmid. We acknowledge support from the INSERM and the Versailles Saint-Quentin University, ANR-13-ISV3-0007,RESPISYNCYCELL,Partenaires cellulaires du virus respiratoire syncytial(2013), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017)
Nature Communications
Nature Communications, Nature Publishing Group, 2017, 8 (1), pp.563. ⟨10.1038/s41467-017-00655-9⟩
Nature Communications (8), 1-11. (2017)
Nature Communications, 2017, 8 (1), pp.563. ⟨10.1038/s41467-017-00655-9⟩
ISSN: 2041-1723
DOI: 10.1038/s41467-017-00655-9
Popis: Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term “IB-associated granules” (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.
Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.
Databáze: OpenAIRE