Longer and shorter forms of Sendai virus C proteins play different roles in modulating the cellular antiviral response.
The Sendai virus (SeV) C gene codes for a nested set of four C proteins that carry out several functions, including the modulation of viral RNA synthesis and countering of the cellular antiviral response. Using mutant C genes (and in particular a C gene with a deletion of six amino acids present only in the larger pair of C proteins) and recombinant SeV carrying these mutant C genes, we find that the nested set of C proteins carry out a nested set of functions. All of the C proteins interdict interferon (IFN) signaling to IFN-stimulated genes (ISGs) and prevent pY701-Stat1 formation. However, only the larger C proteins can induce STAT1 instability, prevent IFN from inducing an antiviral state, or prevent programmed cell death. Remarkably, interdiction of IFN signaling to ISGs and the absence of pY701-Stat1 formation did not prevent IFN-alpha from inducing an anti-Vesicular stomatitis virus (VSV) state. It is possible that IFN-alpha signaling to induce an anti-VSV state can occur independently of the well-established Jak/Stat/ISGF3 pathway and that it is this parallel pathway that is targeted by the longer C proteins.
Garcin
D
D
Department of Genetics and Microbiology, University of Geneva School of Medicine, CH1211 Geneva, Switzerland.
Curran
J
J
Itoh
M
M
Kolakofsky
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology; D053613:Janus Kinase 1; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis; D018108:Respirovirus / Q000378:metabolism / Q000502:physiology*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; C494228:Isgf3g protein, mouse; D020033:Protein Isoforms; D012367:RNA, Viral; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1