title: [Molecular mechanisms for suppression of interferon signal transduction pathways caused by viral infections].
abstract: In order to establish infection to host cells, viruses suppress or escape from the host immune response against microorganisms by various strategies. Interferon (IFN) system is an important contributor of innate immunity. IFN is induced by viral infection, and it promotes antiviral state through induction and/or activation of the effector molecules. Many viruses possess the suppression or inhibition mechanisms for the anti-viral effector molecules, whereas they also perform inhibition of IFN signaling pathway, JAK/STAT pathway. We consider that latter is a most effective strategy counteracting IFN function, because the signaling pathway is an entrance of the system. The strategies counteracting JAK/STAT pathway are varied among virus species. Viruses perform (i) production of IFN-binding protein, (ii) degradation of JAK/STAT components, (iii) suppression of activation (phosphorylation) of the components, (iv) inhibition of nuclear translocation of activated transcription factor, and (v) induction of host JAK/STAT negative regulator. Here, we present these strategies, especially our recent resulta of HSV1, mumps virus, and measles virus. For example, HSV1 induces a host JAK/STAT negative regulator SOCS3 (suppressor of cytokine signaling-3). Mumps virus V protein promotes degradation of both STAT-1 and STAT-3. Measles virus freezes the flexibility of IFN-alpha receptor complex by the action of viral proteins, C and V.
authors.affiliation: Department of Microbiology, Sapporo Medical University, School of Medicine, Chuo-ku, Sapporo. fujii@sapmed.ac.jp
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yokota
authors.forename: Noriko
authors.initials: N
authors.lastname: Yokosawa
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D018259:Herpesvirus 1, Human; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000096:biosynthesis / Q000502:physiology*; D053613:Janus Kinase 1; D008459:Measles virus; D009109:Mumps virus; D010750:Phosphoproteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D017471:Receptors, Interferon; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C069181:V protein, measles virus; D014764:Viral Proteins; D007372:Interferons; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1