title: IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity.
abstract: BACKGROUND
  Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded.
  
  
  RESULTS
  In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles.
  
  
  CONCLUSIONS
  The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses.
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. kevin.tartour@ens-lyon.fr.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. kevin.tartour@ens-lyon.fr.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. kevin.tartour@ens-lyon.fr.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. kevin.tartour@ens-lyon.fr.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. kevin.tartour@ens-lyon.fr.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tartour
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. romain.appourchaux@ens-lyon.fr.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. romain.appourchaux@ens-lyon.fr.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. romain.appourchaux@ens-lyon.fr.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. romain.appourchaux@ens-lyon.fr.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. romain.appourchaux@ens-lyon.fr.
authors.forename: Romain
authors.initials: R
authors.lastname: Appourchaux
authors.affiliation: Plateforme des Microscopies, PPF ASB, Université F. Rabelais et CHRU de Tours, Tours, France. julien.gaillard@univ-tours.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Gaillard
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. xuan-nhi.nguyen@ens-lyon.fr.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. xuan-nhi.nguyen@ens-lyon.fr.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. xuan-nhi.nguyen@ens-lyon.fr.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. xuan-nhi.nguyen@ens-lyon.fr.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. xuan-nhi.nguyen@ens-lyon.fr.
authors.forename: Xuan-Nhi
authors.initials: XN
authors.lastname: Nguyen
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. steffdurand@gmail.com.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. steffdurand@gmail.com.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. steffdurand@gmail.com.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. steffdurand@gmail.com.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. steffdurand@gmail.com.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Durand
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. jocelyn.turpin@ens-lyon.fr.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. jocelyn.turpin@ens-lyon.fr.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. jocelyn.turpin@ens-lyon.fr.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. jocelyn.turpin@ens-lyon.fr.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. jocelyn.turpin@ens-lyon.fr.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Turpin
authors.affiliation: INSERM U966, Université F. Rabelais et CHRU de Tours, Tours, France. elodie.beaumont@univ-tours.fr.
authors.forename: Elodie
authors.initials: E
authors.lastname: Beaumont
authors.affiliation: INSERM U966, Université F. Rabelais et CHRU de Tours, Tours, France. emmanuelle.roch@univ-tours.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Roch
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. gregory.berger@kcl.ac.uk.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. gregory.berger@kcl.ac.uk.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. gregory.berger@kcl.ac.uk.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. gregory.berger@kcl.ac.uk.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. gregory.berger@kcl.ac.uk.|Present address: Department of Infectious Diseases, King's College London School of Medicine, London, SE1 9RT, UK. gregory.berger@kcl.ac.uk.
authors.forename: Gregory
authors.initials: G
authors.lastname: Berger
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. renaud.mahieux@ens-lyon.fr.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. renaud.mahieux@ens-lyon.fr.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. renaud.mahieux@ens-lyon.fr.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. renaud.mahieux@ens-lyon.fr.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. renaud.mahieux@ens-lyon.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
authors.affiliation: INSERM U966, Université F. Rabelais et CHRU de Tours, Tours, France. brand@med.univ-tours.fr.
authors.forename: Denys
authors.initials: D
authors.lastname: Brand
authors.affiliation: Plateforme des Microscopies, PPF ASB, Université F. Rabelais et CHRU de Tours, Tours, France. roingeard@med.univ-tours.fr.|INSERM U966, Université F. Rabelais et CHRU de Tours, Tours, France. roingeard@med.univ-tours.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
authors.affiliation: CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France. acimarel@ens-lyon.fr.|INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France. acimarel@ens-lyon.fr.|Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France. acimarel@ens-lyon.fr.|CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France. acimarel@ens-lyon.fr.|University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France. acimarel@ens-lyon.fr.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cimarelli
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D019065:Virus Assembly; D053586:Virus Internalization
chemical_list: D000943:Antigens, Differentiation; D000998:Antiviral Agents; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C062010:leu-13 antigen