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呼吸道合胞病毒感染细胞中细胞质包涵体的功能组织

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

作者信息

Rincheval Vincent, Lelek Mickael, Gault Elyanne, Bouillier Camille, Sitterlin Delphine, Blouquit-Laye Sabine, Galloux Marie, Zimmer Christophe, Eleouet Jean-François, Rameix-Welti Marie-Anne

机构信息

UMR1173, INSERM, Université de Versailles St. Quentin, Montigny le Bretonneux, 78180, France.

Institut Pasteur Unité Imagerie et Modélisation, CNRS UMR 3691; C3BI, USR 3756, IP CNRS, Paris, 75015, France.

出版信息

Nat Commun. 2017 Sep 15;8(1):563. doi: 10.1038/s41467-017-00655-9.

Abstract

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.

摘要

呼吸道合胞病毒感染细胞会诱导细胞质包涵体(IBs)的形成,病毒RNA聚合酶复合体的所有组分都集中在这些包涵体中。然而,这些包涵体的确切组织结构和功能仍不清楚。在本研究中,我们使用传统成像和超分辨率成像来剖析包涵体的内部结构。我们观察到新合成的病毒mRNA和病毒转录抗终止因子M2-1集中在包涵体亚区室中,我们将其称为“与包涵体相关的颗粒”(IBAGs)。相比之下,病毒基因组RNA、核蛋白、L聚合酶及其辅因子P被排除在IBAGs之外。实时成像显示IBAGs是高度动态的结构。我们的数据表明包涵体是病毒RNA合成的主要场所。数据还进一步表明,在包涵体中合成后不久,病毒mRNA和M2-1在到达细胞质之前会短暂地集中在IBAGs中,并提示了M2-1一种新的转录后功能。呼吸道合胞病毒(RSV)诱导形成包涵体(IBs)以庇护病毒RNA合成。在此,兰切瓦尔等人鉴定出高度动态的与包涵体相关的颗粒(IBAGs),这些颗粒积累新合成的病毒mRNA和病毒M2-1蛋白,但排除病毒基因组RNA和RNA聚合酶复合体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbea/5601476/13a71a9b1d6b/41467_2017_655_Fig9_HTML.jpg

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