2003 Fiscal Year Final Research Report Summary
Mechanism by which Sendai virus inhibits interferon signaling
| Project/Area Number |
13670294
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | 福井医科大学 |
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Principal Investigator |
GOTOH Bin University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (00211920)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Kenji University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助手 (40236419)
KOMATSU Takayuki University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助手 (20215388)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Sendai virus / C protein / accessory proteins / STAT1 / STAT2 / Interferon / signaling / phosphorylation |
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| Research Abstract |
Infection with Sendai virus (SeV) renders cells unresponsive to interferon (IFN). The antagonism to IFN is due to the functions of C protein, which is viral accessory protein encoded by the SeV P gene. Our studies have revealed a molecular basis for the mechanism by which SeV inhibits IFN signaling : 1. SeV C protein binds to the signal transducer and activator of transcription (STAT) 1, a key factor on the IFN signaling pathways, resulting in formation of C-STAT1 high molecular mass complexes under the law salt conditions. 2. The C-terminal half domain of the C protein interacts with the N-terminal domain of STAT1. 3.C protein affects IFN-stimulated phosphorylation of STATs including STAT1, STAT2, and STAT3. 4. C protein impairs the STAT1 dephosphorylation event. 5. Binding of IFN-α to the type I IFN receptor on the cell surface causes tyrosine phosphorylation of STAT1 and STAT2. The IFN-α stimulated tyrosine phosphorylation of STAT2 is completely inhibited by C protein. This complete inhibition is essential for the blockade of IFN-α signaling. 6. Mechanism by which C protein inhibits the IFN-γ response is different from the anti-IFN-α mechanism. C protein allows STAT1 to be phosphorylated at both Tyr^<701> and Ser^<727>. The C-terminal half fragment of C protein, which has the anti-IFN-γ ability comparable to that of the full-size C, prevents the gamma-activated factor (GAF) from binding to a gamma-activated sequence (GAS) site in vitro. This suggests the possibility that the C protein inhibits the GAF-GAS binding through the interaction with STAT1. 7. We found that a C variant with no STAT1-binding property could inhibit the IFN-γ response but not the IFN-α response. This novel mechanism independent of the STAT1-binding remains to be solved.
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Research Products
(14 results)
