Human MX1 orchestrates the cytoplasmic sequestration of neosynthesized influenza A virus vRNPs
Abstract
Interferon-inducible Myxovirus resistance 1 (MX1) proteins are known to restrict influenza A virus (IAV) transcription/replication process. Herein, we show that this early restriction was only partial against human IAVs, with later replication stages more strongly inhibited. Murine (Mm)Mx1 induced an abnormal nuclear accumulation of the viral nucleoprotein (NP) at late time points postinfection. This block was observed to a lower extent with human (Hs)MX1; however, HsMX1 strongly impacted cytoplasmic trafficking of de novo synthesized viral ribonucleoprotein complexes (vRNPs). Indeed, live imaging experiments revealed a transient association of HsMX1 with Rab11a-associated vRNPs, which induced their clustering and their dynein-dependent retrograde transport toward the microtubule organizing center (MTOC). There, vRNPs remained sequestrated together with cellular cofactors YBX1 and Rab11a in large clusters, while MX1 dissociated from them. Dynein inhibition prevented the vRNP clustering and sequestration and significantly rescued infectious IAV production in the presence of HsMX1. In conclusion, this study provides evidence of IAV vRNPs being rerouted and accumulated away from the plasma membrane through the coordinated action of HsMX1 restriction factor, dynein, and the microtubule network.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Joe McKellar
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Jimmy Cadènes
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Francisco García de Gracia
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Corentin Aubé
Université Paris Cité, CNRS, INSERM, Institut Cochin
Ana Luiza Chaves Valadão
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Marine Tauziet
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Mary Arnaud-Arnould
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Antoine Rebendenne
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Lenka Kociánová
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Emmanuel Labaronne
Laboratoire de Biologie et Modélisation de la Cellule (LBMC), Lyon University, Ecole Normale Supérieure (ENS) de Lyon, CNRS UMR 5239, INSERM U1293
Emiliano P. Ricci
Laboratoire de Biologie et Modélisation de la Cellule (LBMC), Lyon University, Ecole Normale Supérieure (ENS) de Lyon, CNRS UMR 5239, INSERM U1293
Bénédicte Delaval
Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), UMR 5237, CNRS, Montpellier University
Raphaël Gaudin
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Nadia Naffakh
Sarah Gallois-Montbrun
Olivier Moncorgé
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University
Caroline Goujon
Institut de Recherche en Infectiologie de Montpellier (IRIM), UMR 9004, CNRS, Montpellier University