title: IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread.
abstract: The interferon-induced transmembrane (IFITM) proteins protect cells from diverse virus infections by inhibiting virus-cell fusion. IFITM proteins also inhibit HIV-1 replication through mechanisms only partially understood. We show that when expressed in uninfected lymphocytes, IFITM proteins exert protective effects during cell-free virus infection, but this restriction can be overcome upon HIV-1 cell-to-cell spread. However, when present in virus-producing lymphocytes, IFITM proteins colocalize with viral Env and Gag proteins and incorporate into nascent HIV-1 virions to limit entry into new target cells. IFITM in viral membranes is associated with impaired virion fusion, offering additional and more potent defense against virus spread. Thus, IFITM proteins act additively in both productively infected cells and uninfected target cells to inhibit HIV-1 spread, potentially conferring these proteins with greater breadth and potency against enveloped viruses.
authors.affiliation: Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France. Electronic address: alex.compton@pasteur.fr.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Compton
authors.affiliation: Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France.
authors.forename: Timothée
authors.initials: T
authors.lastname: Bruel
authors.affiliation: Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Porrot
authors.affiliation: Institut Pasteur, Imagopole, Ultrastructural Microscopy Platform, Paris 75015, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Mallet
authors.affiliation: Institut Pasteur, Imagopole, Ultrastructural Microscopy Platform, Paris 75015, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Sachse
authors.affiliation: Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; École Normale Supérieure, Department of Biology, Cachan 94230, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Euvrard
authors.affiliation: Lady Davis Institute, McGill AIDS Centre, Montreal, QC H3T 1E2, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.affiliation: Institut Pasteur, Department of Virology, Virus & Immunity Unit, Paris 75015, France; CNRS URA 3015, Paris 75015, France; Vaccine Research Institute, Creteil 94010, France. Electronic address: schwartz@pasteur.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D000943:Antigens, Differentiation; D015683:Gene Products, gag; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C062010:leu-13 antigen