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Proc Natl Acad Sci USA. Interferon induction of IFITM proteins promotes infection by human coronavirus OC43

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  • Proc Natl Acad Sci USA. Interferon induction of IFITM proteins promotes infection by human coronavirus OC43

    [Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

    Interferon induction of IFITM proteins promotes infection by human coronavirus OC43

    Xuesen Zhao<SUP>a</SUP>,<SUP>b</SUP>, Fang Guo<SUP>a</SUP>, Fei Liu<SUP>a</SUP>, Andrea Cuconati<SUP>b</SUP>, Jinhong Chang<SUP>a</SUP>, Timothy M. Block<SUP>a</SUP>,<SUP>b</SUP>, and Ju-Tao Guo<SUP>a</SUP><SUP>1</SUP>
    Author Affiliations: <SUP>a</SUP>Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902; and <SUP>b</SUP>Baruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA 18902

    Edited* by Thomas Shenk, Princeton University, Princeton, NJ, and approved April 2, 2014 (received for review November 5, 2013)


    Here we report that all three types of IFNs, the primary mediators of host innate and adaptive antiviral responses, promote infection by human coronavirus HCoV-OC43. They do so through the IFN-induced transmembrane proteins that normally restrict a broad spectrum of viruses but serve as entry factors for HCoV-OC43 to infect its host cells. Our finding reveals a unique mechanism by which HCoV-OC43 evades host antiviral immune responses and suggests that the cytokine response to infection or noninfectious stimuli can be co-opted to promote the infection and spreading of opportunistic pathogens that have evolved adaptations similar to that of HCoV-OC43.


    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.

    evasion of IFN response - viral pathogenesis - proviral function of IFITM


    <SUP>1</SUP>To whom correspondence should be addressed. E-mail:

    Author contributions: X.Z. and J.-T.G. designed research; X.Z., F.G., and F.L. performed research; X.Z., F.G., A.C., J.C., T.M.B., and J.-T.G. analyzed data; and X.Z., A.C., J.C., and J.-T.G. wrote the paper.

    The authors declare no conflict of interest.

    *This Direct Submission article had a prearranged editor.

    This article contains supporting information online at