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SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3- TBK1 complex

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Protein & Cell 2014年第5期5卷 369-381页

作者： Xiaojuan chen Xingxing Yang Yang Zheng Yudong Yang Yaling Xing zhongbin chen Division of Infection and Immunity Department of Electromagnetic and Laser Biology Beijing Institute of Radiation Medicine_ Beijing 100850 China Anhui Medical University Hefei 230032 China

SARS coronavirus （SARS-CoV） develops an antagonis- tic mechanism by which to evade the antiviral activities of interferon （IFN）. Previous studies suggested that SARS-CoV papain-like protease （PLpro） inhibits activa- tion of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism（s） used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro effi- ciently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain （PLpro-TM） from SARS-CoV inhibits STING/ TBKl/IKKE-mediated activation of type I IFNs and dis- rupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBKI. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKK~, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activa- tion of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is dis- rupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3- TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction withSTING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.

关键词： SARS coronavirus papain-like protease,interferon deubiquitinase STING-TRAF3-TBK1 complex

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Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclinl to negatively regulate antiviral innate immunity

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Protein & Cell 2014年第12期5卷 912-927页

作者： Xiaojuan chen Kai Wang Yaling Xing Jian Tu Xingxing Yang Qian Zhao Kui Li zhongbin chen Division of Infection and Immunity Department of Electromagnetic and Laser Biology Beijing Institute of Radiation Medicine Beijing 100850 China Department of Immunology Bengbu Medical College Bengbu 233030 China Prince of Wales Clinical School The University of New South Wales Sydney NSW 2052 Australia Department of Microbiology Immunology and Biochemistry University of Tennessee Health Science Center Memphis TN 38163 USA

Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 （PLP2-TM） of coronaviruses acts as a novel autophagy- inducing protein. Intriguingly, PLP2-TM induces incom- plete autophagy process by increasing the accumula- tion of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2- TM interacts with the key autophagy regulators, LC3 and Beclinl, and promotes Beclinl interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclinl partially reverses PLP2-TM＇s inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results sug- gested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclinl, which in turn modulates coronavirus replication and antiviral innate immunity.

关键词： coronavirus papain-like proteaseautophagy antiviral immunity Beclinl STING

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Effect of antisense oligonucleotides targeting telomerase catalytic subunit on tumor cell proliferation in vitro

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Chinese Science Bulletin 2002年第12期47卷 993-997页

作者： Shengqi Wang Li Lin zhongbin chen Ruxian Lin Suhong chen Wei Guan Xiaohong Wang Beijing Inst Radiat Med Beijing 100850 Peoples R China

To screen specific antitumor drugs targeting telomerase catalytic subunit (hEST2), 12 different hEST2 antisense oligonucleotides were designed based on hEST2 mRNA second structure and transfected into tumor cell lines by the lipofectin-mediated method. Cell growth activity was evaluated by MTT assay. HEST212 was picked out and its specificity, antitumor tree and continuous effect were analyzed. The results showed that hEST212 had promising anti-tumor activity in vitro, hEST2 can be used as a pratical target and an antisense drug candidate for cancer.

关键词： telomerase HEST2 tumor antisense oligonucleotides.

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The Life-Cycle Model with Optimal Individual Years of Schooling and Simulation

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数学计算（中英文版） 2014年第2期3卷 44-48页

作者： Donghan Cai Huan Yang zhongbin chen College of Math. & Stat. Wuhan Univ. Wuhan 430072 PR. China School of Econ. & Management Wuhan Univ. Wuhan 430072 P.R. China

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A New Type Power Converter and Its Application Prospect in Industry

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Journal of Electromagnetic Analysis and Applications 2011年第3期3卷 94-100页

作者： Wenhua Hu Pinggang Song zhongbin chen Qianzhi Zhou 不详

A new type power convertsion mode is structured by combineing switch power conversion mode with linear amplifica-tion mode, so as to acquire their integrated optimal performances. The theoretical analyses and experimental results are presented in this paper. They are proved that the new type converter can match many kinds of loads, including nonlinear loads, with strong robustness, good waveforms and high efficiency. Its application prospect in industry can be expected, particularly for the conditions where serious static and dynamic performances are required.

关键词： Power Converter SLH Performances Nonlinear Loads Industry

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Proteolytic Processing,Interferon antagonist and Deubiquitinase Activies of the Papain-like Protease of the New Emerging Middle East Respiratory Syndrome Coronavirus

Proteolytic Processing,Interferon antagonist and Deubiquitin...

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第八届全国医学生物化学与分子生物学第五届全国临床应用生物化学与分子生物学2013华东六省一市生物化学与分子生物学联合学术研讨会

作者： Xingxing Yang Xiaojuan chen Yaling Xing zhongbin chen Division of Infection and Immunity Beijing Institute of Radiation Medicine Beijing Institute of Radiation Medicine Anhui Medical University

The newly emergent Middle East respiratory syndrome coronavirus(MERS-CoV)causes severe pulmonary disease in human beings,represents the second example of a highly pathogenic coronavirus followed by the first of *** studies revealed that only two viral proteases,papain-like protease(PLpro)and 3C-like protease(3CLpro),which process the polyproteins encoded by the MERS-CoV genomic *** previously showed that SARS-CoV

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Coronavirus papain-like proteases induce autophagy but block autophagosome fusion with lysosomes through interacting with Beclinl

Coronavirus papain-like proteases induce autophagy but block...

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细胞—生命的基础——中国细胞生物学学会2013年全国学术大会·武汉

作者： zhongbin chen Kai Wang Xiaojuan chen Yaling Xing Xingxing Yang Beijing Institute of Radiation Medicine

Autophagy is a cellular catabolic process that sequesters cargo in double-membraned autophagosome and delivers the cargo to lysosomes to be degraded for recycling resource for *** plays important roles in modulating viral replication and antiviral innate and adaptive immune response. Previous studies demonstrated that coronavirus infection is associated with the autophagic process,

关键词： Coronavirus NL63 Papain-like protease Autophagy Beclinl STING

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高等教育融资困境与融资制度研究

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江苏高教 2006年第2期 56-58页

作者：陈忠斌上海财经大学

高等教育大众化进程面临融资困境,有效的融资制度安排供给不足是主要原因。政府在高等教育融资制度安排变迁与创新中占据主导性地位,应当发挥公共财政在建立公共投融资体制中的主导和引导作用。市场机制对高等教育融资制度安排的变迁和... 详细信息

高等教育大众化进程面临融资困境,有效的融资制度安排供给不足是主要原因。政府在高等教育融资制度安排变迁与创新中占据主导性地位,应当发挥公共财政在建立公共投融资体制中的主导和引导作用。市场机制对高等教育融资制度安排的变迁和创新具有决定性的作用。

关键词：高等教育公共投融资市场型融资制度安排

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Coronavirus papain-like proteases induce incomplete autophagy through interacting with Beclin 1 to negatively regulate antiviral innate immunity

Coronavirus papain-like proteases induce incomplete autophag...

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第九届全国免疫学学术大会

作者： zhongbin chen Xiaojuan chen Kai Wang Yaling Xing Xingxing Yang Qian Zhao Beijing Institute of Radiation Medicine

Autophagy plays important roles in modulating viral replication and antiviral immune *** infection is associated with the autophagic process,however,little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate ***,we show that the membrane-associated papain-like protease PLP2(PLP2-TM)of coronaviruses acts as a novel autophagy-inducing ***,PLP2-TM induces incomplete autophagy process by increasing the accumulation of autophagosomes but blocking the fusion of autophagosomes with ***,PLP2-TM interacts with the key autophagy regulators,LC3 and Beclinl,and promotes Beclinl interaction with STING,the key regulator for antiviral IFN ***,Knockdown of Beclin 1partially reverses PLP2-TM’s inhibitory effect on innate immunity which resulting in decreased coronavirus *** results suggested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclin 1,which in turn modulates coronavirus replication and antiviral innate immunity.

关键词： Coronavirus Papain-like protease Autophagy Antiviral immunity Beclinl STING

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5'-triphosphate-siRNA against survivin gene induces interferon production and inhibits proliferation of lung cancer cells in vitro

5'-triphosphate-siRNA against survivin gene induces interfer...

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第九届全国免疫学学术大会

作者： Yaling Xing Xiaojuan chen Kai Wang Fei Yan Xingxing Yang zhongbin chen Beijing Institute of Radiation Medicine

Survivin is a new member of the inhibitors of apoptosis(IAPs)family and upregulated in various human malignancies including human lung *** this study,we proposed a new strategy for RNA interference(RNAi)-mediated anticancer therapy that combining activation of IFN production with RNAi using 5’-triphosphate-siRNA(3p-siRNA)against survivin *** designed and generated 3p-siRNA targeting human survivin gene(3p-survivin-siRNA).The findings reported here demonstrated that 3p-survivin-siRNA induced a 3p-dependent type-I IFN response when transfected into human lung cancer *** 3p-survivin-siRNA significantly inhibited lung cancer cell proliferation in a 3p-dependent *** anticancer effect of 3p-survivin-siRNA was superior to that of conventional *** expression level of survivin in 3p-survivin-siRNA-treated A549 cells was significantly lower than that of ***,when 3p-survivin-siRNA silencing approach was combined with radiation treatment,3p-survivin-siRNA increases the cytotoxicity of A549 cells and induces more cells underwent *** conclusion,our results suggest that 3p-survivin-siRNA could act as a powerful bifunctional molecule with potential for developing promising radiosensitization therapeutics against human lung cancer.

关键词： 5’-triphosphated siRNA IFNa/b lung cancer cell RNAi survivin

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