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- 2016
西西里病毒抑制Ⅰ型干扰素的产生机制
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Abstract:
西西里病毒属布尼亚病毒科白蛉病毒属．在病毒感染机体过程中, 病毒非结构蛋白可特异性靶向细胞内相关因子, 阻断或抑制宿主天然免疫信号通路的激活．利用双报告基因检测系统, 发现西西里病毒非结构蛋白可抑制Ⅰ型干扰素的产生, 通过免疫共沉淀分析, 证实该现象不依赖于TBK1, 并首次发现了西西里病毒非结构蛋白通过蛋白酶体依赖的途径降解宿主相关因子, 进而抑制Ⅰ型干扰素表达这一机制．这一结果为更好地了解西西里病毒致病机理及相关治疗药物的研发提供了理论支持．
Sand?y fever Sicilian virus(SFSV)is a member of the Phlebovirus of Bunyavirus family. After the virus infects humans, non-structural (NSs) proteins of virus can target specific cellular proteins to counteract or inhibit the host innate immune signal action. In this study, it is found through luciferase reporter assays that the NSs proteins of SFSV inhibit activation of IFN-β promoter. Through co-immunoprecipitation assay, it is proved that SFSV NSs pro-tein inhibiting typeⅠinterferon is not dependent on TBK1. It is discovered for the first time that the SFSV NSs pro-tein inhibits typeⅠinterferon via degradation of factors through the proteasome-dependent pathway. This research provides a better understanding of typeⅠIFN counteracting mechanisms and novel therapeutic approaches for serious pathogens
| [1] | Gori-Savellini G, Valentini M, Cusi M G, et al. Toscana virus NSs protein inhibits the induction of type I interferon by interacting with RIG-I[J]. <i>Journal of Virology</i>, 2013, 87(12):6660-6667. |
| [2] | Blakqori G, Delhaye S, Habjan M, et al. La Crosse bunyavirus nonstructural protein NSs serves to suppress the typeⅠinterferon system of mammalian hosts[J]. <i>Journal of Virology</i>, 2007, 81(10):4991- 4999. |
| [3] | van Knippenberg I, Calton-Smith C, Elliott R M, et al. The N-terminus of Bunyamwera orthobunyavirus NSs protein is essential for interferon antagonism[J]. <i>J</i> <i>Gen Virol</i>, 2010, 91(8):2002-2006. |
| [4] | age, proteasomal degradation and sequestration:Three mechanisms of viral subversion of typeⅠinterferon responses[J]. <i>Innate Immun</i>, 2009, 1(6):599-606. |
| [5] | Spiropoulou C F, Albari？o C G, Ksiazek T G, et al. Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling[J]. <i>Journal of Virology</i>, 2007, 81(6):2769-2776. |
| [6] | Weber F, Bridgen A, Fazakerley J K, et al. Bunyamwera bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon[J]. <i>Journal of Virology</i>, 2002, 76(16):7949-7955. |
| [7] | May N L, Dubaele S, Santis L P D, et al. TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus[J]. <i>Cell</i>, 2004, 116(4):541-550. |
| [8] | Samuel C E. Antiviral actions of interferons[J]. <i>Clin Microbiol Rev</i>, 2001, 14(4):778-809. |
| [9] | Mibayashi M, Martinez-Sobrido L, Loo Y M, et al. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus[J]. <i>Journal of Virology</i>, 2007, 81(2):514 -524. |
| [10] | Ning Y J, Wang M, Deng M, et al. Viral suppression of innate immunity via spatial isolation of TBK1/IKKepsilon from mitochondrial antiviral platform[J]. <i>Mol Cell Biol</i>, 2014, 6(4):324-337. |
| [11] | Taylor K E, Mossman K L. Advances in understanding viral evasion of type I interferon[J]. <i>Immunology</i>, 2013, 138(3):190-197. |
| [12] | Shi X, van Mierlo J T, French A, et al. Visualizing the replication cycle of bunyamwera orthobunyavirus expressing fluorescent protein-tagged Gc glycoprotein[J]. <i>Journal of Virology</i>, 2010, 84(17):8460-8469. |
| [13] | Thompson M R, Kaminski J J, Kurt-Jones E A, et al. Pattern recognition receptors and the innate immune response to viral infection [J]. <i>Viruses</i>, 2011, 3(6):920-940. |
| [14] | Stark G R, Kerr I M, Williams B R, et al. How cells respond to interferons[J]. <i>Biochem</i>, 1998, 67:227-264. |
| [15] | Billecocq A, Spiegel M, Vialat P, et al. NSs protein of Rift Valley fever virus blocks interferon production by inhibiting host gene transcription[J]. <i>Journal of Virology</i>, 2004, 78(18):9798-9806. |
| [16] | García-Sastre A, Biron C A. Type 1 interferons and the virus-host relationship:A lesson in détente[J]. <i>Science</i>, 2006, 312(5775):879-882. |
| [17] | Yoneyama M, Onomoto K, Jogi M, et al. Viral RNA detection by RIG-l-like receptors[J]. <i>Current Opinion Immunology</i>, 2015, 32:48-53. |
| [18] | Haller O, Kochs G, Weber F, et al. The interferon response circuit:Induction and suppression by pathogenic viruses[J]. <i>Virology</i>, 2006, 344(2006):119-130. |
| [19] | Opitz B, Rejaibi A, Dauber B, et al. IFN-beta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1[J]. <i>Protein Cell Microbio</i>, 2007, 9(4):930 -938. |
| [20] | Mclnerney G M, Karlsson Hedestam G B. Direct cleav- |
