title: Phosphoproteome characterization reveals that Sendai virus infection activates mTOR signaling in human epithelial cells.
abstract: Sendai virus (SeV) is a common respiratory pathogen in mice, rats, and hamsters. Host cell recognition of SeV is mediated by pathogen recognition receptors, which recognize viral components and induce intracellular signal transduction pathways that activate the antiviral innate immune response. Viruses use host proteins to control the activities of signaling proteins and their downstream targets, and one of the most important host protein modifications regulated by viral infection is phosphorylation. In this study, we used phosphoproteomics combined with bioinformatics to get a global view of the signaling pathways activated during SeV infection in human lung epithelial cells. We identified altogether 1347 phosphoproteins, and our data shows that SeV infection induces major changes in protein phosphorylation affecting the phosphorylation of almost one thousand host proteins. Bioinformatics analysis showed that SeV infection activates known pathways including MAPK signaling, as well as signaling pathways previously not linked to SeV infection including Rho family of GTPases, HIPPO signaling, and mammalian target of rapamycin (mTOR)-signaling pathway. Further, we performed functional studies with mTOR inhibitors and siRNA approach, which revealed that mTOR signaling is needed for both the host IFN response as well as viral protein synthesis in SeV-infected human lung epithelial cells.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Öhman
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.|Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Söderholm
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Maruthibabu
authors.initials: M
authors.lastname: Paidikondala
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Lietzén
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Tuula A
authors.initials: TA
authors.lastname: Nyman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019295:Computational Biology; D006224:Cricetinae; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D010253:Respirovirus Infections / Q000378:metabolism* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029082:Sendai virus / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D010750:Phosphoproteins; D012333:RNA, Messenger; D007372:Interferons; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Bioinformatics; IFN response; Phosphoproteome; Virus infection; mTOR signaling