title: Human respiratory syncytial virus infection is inhibited by IFN-induced transmembrane proteins.
abstract: The IFN immune system plays an essential role in protecting the host against most viral infections. In order to explore the interactions between the IFN pathway and human respiratory syncytial virus (RSV) infection, and to identify potential IFN-stimulated genes (ISGs) that may be involved in suppressing the replication of RSV, we utilized an IFN pathway-specific microarray to study the effects of RSV infection on the IFN pathway in HeLa cells. We showed that RSV infection enhanced the expression of a series of ISGs, including oligoadenylate synthetase 2, IFITM1 (IFN-induced transmembrane protein 1) and myxovirus resistance 2. Our results also showed that the IFITM proteins potently inhibited RSV infection mainly by interfering with both virus entry and the subsequent replication steps, but not the attachment process. The antiviral effect of IFITM3 was not affected by ubiquitination modification. Furthermore, knocking down the endogenous and IFN-induced expression of IFITM1 and 3 facilitated RSV infection. Expression of the IFITM proteins was found to delay the phosphorylation of IFN regulatory factor 3 through interfering with the detection of viral RNA by MDA5 (melanoma differentiation-associated gene 5) and RIG-I (retinoic acid-inducible gene I). These results demonstrated that the restriction of RSV infection by the IFITM proteins was achieved through the inhibition of virus entry and replication, and they provided further insight for exploring the mechanism of IFITM-protein-mediated virus restriction.
authors.affiliation: University of Chinese Academy of Sciences, PR China.|Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yanlu
authors.initials: Y
authors.lastname: Zan
authors.affiliation: University of Chinese Academy of Sciences, PR China.|Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Du
authors.affiliation: University of Chinese Academy of Sciences, PR China.|Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Po
authors.initials: P
authors.lastname: Tien
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics; D053586:Virus Internalization; D014779:Virus Replication / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D000998:Antiviral Agents; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C062010:leu-13 antigen; D007372:Interferons; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1