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Phosphatidylserine-Specific Phospholipase A1 is the Critical Bridge for Hepatitis C Virus assembly

Virologica Sinica 2019年第5期34卷 521-537页

作者： Qi Yang Min Guo Yuan Zhou Xue Hu Yun Wang Chunchen Wu Min Yang Rongjuan Pei Xinwen Chen Jizheng Chen Department of Gastroenterology Guangzhou Women and Children's Medical CenterGuangzhou 510623China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China School of Life Science and Technology China Pharmaceutical UniversityNanjing 210009China

The phosphatidylserine-specific phospholipase A1(PLA1A)is an essential host factor in hepatitis C virus(hcv)*** this study,we mapped the E2,NS2 and NS5A involved in PLA1A interaction to their lumenal domains and membranous parts,through which they form oligomeric protein complexes to participate in hcv *** regions of PLA1A were involved in their interaction and complex ***,the results represented structures with PLA1A and E2 in closer proximity than NS2 and NS5A,and strongly suggest PLA1 A-E2,s physical interaction in ***,we mapped the NS5A sequence which participated in PLA1A interaction with the C-terminus of domain ***,these amino acids in the sequence are also essential for viral RNA *** experiments revealed that these four proteins interact with each ***,PLA1A expression levels were elevated in livers from hcv-infected *** conclusion,we exposed the structural determinants of PLA1A,E2,NS2 and NS5A proteins which were important for hcv assembly and provided a detailed characterization of PLA1A in hcv assembly.

关键词： Phosphatidylserine-specific phospholipase A1(PLA1 A) hcv assembly Viral RNA replication

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CD2-associated protein contributes to hcv propagation and steatosis by disrupting insulin signaling

CD2-associated protein contributes to HCV propagation and st...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2...

作者： Huixia Zhang Chao Zhang Hong Tang Shanshan Gao Fang Sun Yuan Yang Weiping Zhou Yu Hu Changshu Ke Yu Wu Zeyang Ding Lin Guo Rongjuan Pei Xinwen Chen Man-Sun Sy Bixiang Zhang Chaoyang Li Center for Molecular Virology Wuhan Institute of VirologyChinese Academy of Sciences University of Chinese Academy of Sciences Key laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of Sciences Institute Pasteur of Shanghai Chinese Academy of Sciences Eastern Hepatobiliary Surgery Hospital Second Military Medical University Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology School of Life Sciences Wuhan UniversityState Key Laboratory of Virology Department of Pathology School of MedicineCase Western Reserve University School of Chemistry Chemical Engineeringand Life SciencesWuhan University of Technology

Chronic hepatitis C virus(hcv) infection can result in steatosis,a condition displaying aberrant accumulation of neutral lipid vesicles,the component of lipid droplets(LDs),which are essential for hcv ***,the interplays between hcv infection and steatosis remain ***,we show that hcv infected cells having higher levels of CD2 associated protein(CD2 AP),which plays two distinct,yet tightly-linked roles in hcv pathogenesis: elevated CD2 AP binding the domain III of NS5 A via its SH3 *** interaction transports NS5 A to LDs via an actin dependent manner to facilitate viral assembly;up-regulated CD2 AP interacting with E3 ligases cbl/cbl-c to degrade insulin receptor substrate 1(IRS1),which in turn disrupts insulin signaling and increases LDs accumulation thru the IRS1-Akt-AMPK-hormone sensitive lipase(HSL) signaling axis to accommodate viral *** hcv infected mouse model and human subjects,CD2 AP expression is up-regulated and the upregulation correlates well with liver *** importantly,hepatocellular carcinoma showed significantly stronger CD2 AP staining than peritumor ***: CD2 AP was identified as a protein upregulated by hcv infection,which in turn stimulated hcv assembly and steatosis by disrupting insulin signaling,targeting CD2 AP may offer an opportunity for alleviating hcv infection and its associated liver pathology.

关键词： CD2AP insulin resistance liver pathology hcv assembly

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