PMID- 29123131 OWN - NLM STAT- MEDLINE DCOM- 20180907 LR - 20181113 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 IP - 1 DP - 2017 Nov 9 TI - Influenza virus genome reaches the plasma membrane via a modified endoplasmic reticulum and Rab11-dependent vesicles. PG - 1396 LID - 10.1038/s41467-017-01557-6 [doi] LID - 1396 AB - Transport of neo-synthesized influenza A virus (IAV) viral ribonucleoproteins (vRNPs) from the nucleus to the plasma membrane involves Rab 11 but the precise mechanism remains poorly understood. We used metal-tagging and immunolabeling to visualize viral proteins and cellular endomembrane markers by electron microscopy of IAV-infected cells. Unexpectedly, we provide evidence that the vRNP components and the Rab11 protein are present at the membrane of a modified, tubulated endoplasmic reticulum (ER) that extends all throughout the cell, and on irregularly coated vesicles (ICVs). Some ICVs are found very close to the ER and to the plasma membrane. ICV formation is observed only in infected cells and requires an active Rab11 GTPase. Against the currently accepted model in which vRNPs are carried onto Rab11-positive recycling endosomes across the cytoplasm, our findings reveal that the endomembrane organelle that is primarily involved in the transport of vRNPs is the ER. FAU - de Castro Martin, Isabel Fernandez AU - de Castro Martin IF AD - Centro Nacional de Biotecnologia, CNB-CSIC, Department of Macromolecular Structures, Cell Structure Lab, 28049, Madrid, Spain. FAU - Fournier, Guillaume AU - Fournier G AD - Departement de Virologie, Institut Pasteur, Unite de Genetique Moleculaire des Virus a ARN, 75015, Paris, France. AD - CNRS, UMR3569, 75015, Paris, France. AD - Universite Paris Diderot, Sorbonne Paris Cite, EA302, 75015, Paris, France. FAU - Sachse, Martin AU - Sachse M AD - Center for Innovation and Technological Research, Ultrastructural Bio-imaging, Institut Pasteur, 75015, Paris, France. FAU - Pizarro-Cerda, Javier AU - Pizarro-Cerda J AD - Departement de Biologie Cellulaire et Infection, Institut Pasteur, Unite des Interactions Bacteries-Cellules, 75015, Paris, France. AD - INSERM, U220 8. INRA, USC 2020, 75015, Paris, France. AD - Unite de Recherche Yersinia, Institut Pasteur, 75015, Paris, France. AD - Centre National de Reference 'Peste et autres Yersinioses', 75015, Paris, France. AD - Centre Collaborateur OMS de Reference et Recherche 'Yersinioses', Institut Pasteur, Unite des Interactions Bacteries-Cellules, 75015, Paris, France. FAU - Risco, Cristina AU - Risco C AD - Centro Nacional de Biotecnologia, CNB-CSIC, Department of Macromolecular Structures, Cell Structure Lab, 28049, Madrid, Spain. crisco@cnb.csic.es. FAU - Naffakh, Nadia AU - Naffakh N AD - Departement de Virologie, Institut Pasteur, Unite de Genetique Moleculaire des Virus a ARN, 75015, Paris, France. nadia.naffakh@pasteur.fr. AD - CNRS, UMR3569, 75015, Paris, France. nadia.naffakh@pasteur.fr. AD - Universite Paris Diderot, Sorbonne Paris Cite, EA302, 75015, Paris, France. nadia.naffakh@pasteur.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171109 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (RNA, Small Interfering) RN - 0 (Ribonucleoproteins) RN - 0 (Viral Proteins) RN - EC 3.6.1.- (rab11 protein) RN - EC 3.6.5.2 (rab GTP-Binding Proteins) SB - IM MH - A549 Cells MH - Animals MH - Cell Membrane/metabolism MH - Dogs MH - Endoplasmic Reticulum/*metabolism MH - Endosomes/metabolism MH - HEK293 Cells MH - Humans MH - Influenza A virus/*genetics MH - Madin Darby Canine Kidney Cells MH - Microscopy, Electron MH - Protein Transport/*physiology MH - RNA Interference MH - RNA, Small Interfering/genetics MH - Ribonucleoproteins/*metabolism MH - Viral Proteins/*metabolism MH - rab GTP-Binding Proteins/genetics/*metabolism PMC - PMC5680169 COIS- The authors declare no competing financial interests. EDAT- 2017/11/11 06:00 MHDA- 2018/09/08 06:00 PMCR- 2017/11/09 CRDT- 2017/11/11 06:00 PHST- 2017/01/13 00:00 [received] PHST- 2017/09/27 00:00 [accepted] PHST- 2017/11/11 06:00 [entrez] PHST- 2017/11/11 06:00 [pubmed] PHST- 2018/09/08 06:00 [medline] PHST- 2017/11/09 00:00 [pmc-release] AID - 10.1038/s41467-017-01557-6 [pii] AID - 1557 [pii] AID - 10.1038/s41467-017-01557-6 [doi] PST - epublish SO - Nat Commun. 2017 Nov 9;8(1):1396. doi: 10.1038/s41467-017-01557-6.