title: Interferon-Induced Transmembrane Protein-Mediated Inhibition of Host Cell Entry of Ebolaviruses.
abstract: Ebolaviruses are highly pathogenic in humans and nonhuman primates and pose a severe threat to public health. The interferon-induced transmembrane (IFITM) proteins can restrict entry of ebolaviruses, influenza A viruses, and other enveloped viruses. However, the breadth and mechanism of the antiviral activity of IFITM proteins are incompletely understood. Here, we employed ebolavirus glycoprotein-pseudotyped vectors and ebolavirus-like particles to address this question. We show that IFITM proteins inhibit the cellular entry of diverse ebolaviruses and demonstrate that type I interferon induces IFITM protein expression in macrophages, major viral targets. Moreover, we show that IFITM proteins block entry of influenza A viruses and ebolaviruses by different mechanisms and provide evidence that antibodies and IFITM proteins can synergistically inhibit cellular entry of ebolaviruses. These results provide insights into the role of IFITM proteins in infection by ebolaviruses and suggest a mechanism by which antibodies, though poorly neutralizing in vitro, might contribute to viral control in vivo.
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen.
authors.forename: Florian
authors.initials: F
authors.lastname: Wrensch
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen Institute for Cellular Chemistry, Hannover Medical School, Germany.
authors.forename: Christina B
authors.initials: CB
authors.lastname: Karsten
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gnirß
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen.
authors.forename: Michael
authors.initials: M
authors.lastname: Winkler
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
authors.affiliation: Infection Biology Unit, German Primate Center, Göttingen.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism*; D002460:Cell Line; D029043:Ebolavirus / Q000378:metabolism / Q000472:pathogenicity*; D006023:Glycoproteins / Q000378:metabolism; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism / Q000472:pathogenicity; D007370:Interferon Type I / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D000943:Antigens, Differentiation; D006023:Glycoproteins; D007370:Interferon Type I; D008565:Membrane Proteins; D014764:Viral Proteins; C062010:leu-13 antigen
keywords: Ebola; IFITM; entry; glycoprotein; interferon