title: Interferon induction of IFITM proteins promotes infection by human coronavirus OC43.
abstract: IFNs are a family of cytokines that are essential for the antiviral response in vertebrates. Not surprisingly, viruses have adapted to encode virulence factors to cope with the IFN response. Intriguingly, we show here that all three types of interferons, IFN-α, IFN-γ, and IFN-λ, efficiently promote infection by a human coronavirus, HCoV-OC43, one of the major etiological agents of common cold, through the induction of IFN-inducible transmembrane (IFITM) proteins. IFITMs typically exert their antiviral function by inhibiting the entry of a broad spectrum of viruses into their host cells, presumably by trapping and degrading invading virions within the endocytic compartments. In contrast, HCoV-OC43 uses IFN-induced human IFITM2 or IFITM3 as an entry factor to facilitate its infection of host cells. Reverse genetics analyses suggest that the structural motifs critical for the IFITM proteins' enhancement of HCoV-OC43 infection are distinct from those required for inhibiting infection by other viruses. We also present evidence showing that IFITM family members work as homo- and hetero-oligomers to modulate virus entry. The observed enhancement of HCoV-OC43 infection by IFNs may underlie the propensity of the virus to invade the lower respiratory tract under inflammatory conditions.
authors.affiliation: Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Andrea
authors.initials: A
authors.lastname: Cuconati
authors.forename: Jinhong
authors.initials: J
authors.lastname: Chang
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.forename: Ju-Tao
authors.initials: JT
authors.lastname: Guo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018352:Coronavirus Infections / Q000209:etiology / Q000276:immunology / Q000821:virology; D028962:Coronavirus OC43, Human / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014774:Virulence / Q000276:immunology; D053586:Virus Internalization
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D007372:Interferons
keywords: evasion of IFN response; proviral function of IFITM; viral pathogenesis
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