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A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication

Signal Transduction and Targeted Therapy 2024年第7期9卷 3112-3129页

作者： Yuzheng Zhou Zongpeng Chen Sijie Liu Sixu Liu Yujie Liao Ashuai Du Zijun Dong Yongxing Zhang Xuan Chen Siyi Tao Xin Wu Aroona Razzaq Gang Xu De-an Tan Shanni Li Youwen Deng Jian Peng Shuyan Dai Xu Deng Xianwen Zhang taijiao jiang Zheng Zhang Gong Cheng Jincun Zhao Zanxian Xia Department of Cell Biology School of Life SciencesCentral South University410013 ChangshaChina Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and Technology518112 ShenzhenChina Department of Basic Medicine School of MedicineHunan Normal University410081 ChangshaChina Department of spine surgery The Third Xiangya HospitalCentral South University410013 ChangshaChina School of Basic Medical Sciences Anhui Medical University230032 HefeiChina Hunan Key Laboratory of Neurorestoratology 921 Hospital of Joint Logistics Support Force People’s Liberation Army of China(The Second Affiliated Hospital of Hunan Normal University)410003 ChangshaHunanChina Department of Geriatric Surgery Xiangya HospitalCentral South University410008 ChangshaChina Xiangya School of Pharmaceutical Sciences Central South University410013 ChangshaChina Institute of Infectious Diseases Shenzhen Bay Laboratory518132 ShenzhenChina Guangzhou Laboratory 510005 GuangzhouChina Tsinghua University-Peking University Joint Center for Life Sciences School of MedicineTsinghua University100084 BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouChina Hunan Key Laboratory of Animal Models for Human Diseases Hunan Key Laboratory of Medical Genetics&Center for Medical GeneticsSchool of Life SciencesCentral South University410008 ChangshaChina

The ORF9b protein,derived from the nucleocapsid’s open-reading frame in both SARS-CoV and SARS-CoV-2,serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune *** its significance,the precise regulatory mechanisms underlying its function remain *** the present study,we unveil that the ORF9b protein of SARS-CoV-2,including emerging mutant strains like Delta and Omicron,can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway,despite certain mutations present among these ***,our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70(TOM70)as a substrate receptor,bridging ORF9b with heat shock protein 90 alpha(HSP90α)and Cullin 5(CUL5)to form a *** this complex,CUL5 triggers the ubiquitination and degradation of ORF9b,acting as a host antiviral factor,while HSP90αfunctions to stabilize ***,treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b,leading to a pronounced inhibition of SARS-CoV-2 ***-cell sequencing data revealed an up-regulation of HSP90αin lung epithelial cells from COVID-19 patients,suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90αto evade the host *** study identifies the CUL5-TOM70-HSP90αcomplex as a critical regulator of ORF9b protein stability,shedding light on the intricate host–virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

关键词： stability modulator offering

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Development of PREDAC-H1pdm to model the antigenic evolution of influenza A/(H1N1)pdm09 viruses

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Virologica Sinica 2023年第4期38卷 541-548页

作者： Mi Liu Jingze Liu Wenjun Song Yousong Peng Xiao Ding Lizong Deng taijiao jiang jiangsu Institute of Clinical Immunology The First Affiliated Hospital of Soochow UniversitySuzhou215006China Institute of Systems Medicine Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100005China Suzhou Institute of Systems Medicine Suzhou215123China Guangzhou Laboratory Guangzhou510005China Bioinformatics Center College of BiologyHunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha410082China State Key Laboratory of Respiratory Disease the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhou510120China

The Influenza A(H1N1)pdm09 virus caused a global pandemic in 2009 and has circulated seasonally ever *** the continual genetic evolution of hemagglutinin in this virus leads to antigenic drift,rapid identification of antigenic variants and characterization of the antigenic evolution are *** this study,we developed PREDAC-H1pdm,a model to predict antigenic relationships between H1N1pdm viruses and identify antigenic clusters for post-2009 pandemic H1N1 *** model performed well in predicting antigenic variants,which was helpful in influenza *** mapping the antigenic clusters for H1N1pdm,we found that substitutions on the Sa epitope were common for H1N1pdm,whereas for the former seasonal H1N1,substitutions on the Sb epitope were more common in antigenic ***,the localized epidemic pattern of H1N1pdm was more obvious than that of the former seasonal H1N1,which could make vaccine recommendation more ***,the antigenic relationship prediction model we developed provides a rapid determination method for identifying antigenic variants,and the further analysis of evolutionary and epidemic characteristics can facilitate vaccine recommendations and influenza surveillance for H1N1pdm.

关键词： H1N1pdm virus Antigenic relationship prediction Antigenic evolution Vaccine recommendation

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Integrated interactome and transcriptome analysis reveals key host factors critical for SARS-CoV-2 infection

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Virologica Sinica 2023年第4期38卷 508-519页

作者： Jie Sheng Lili Li Xueying Lv Meiling Gao Ziyi Chen Zhuo Zhou Jingfeng Wang Aiping Wu taijiao jiang Institute of Systems Medicine Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100005China Suzhou Institute of Systems Medicine Suzhou215123China Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100005China Department of Microbiology and Parasitology College of Basic Medical SciencesChina Medical UniversityShenyang110122China Guangzhou Laboratory Guangzhou510005China State Key Laboratory of Respiratory Disease the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhou510120China

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has seriously threatened global public health and caused huge economic *** studies of SARS-CoV-2 can help understand the interaction between the virus and host,thereby providing a new perspective in guiding the intervention and treatment of the SARS-CoV-2 *** large amount of SARS-CoV-2 omics data have been accumulated in public databases,this study aimed to identify key host factors involved in SARSCoV-2 infection through systematic integration of transcriptome and interactome *** manually curating published studies,we obtained a comprehensive SARS-CoV-2-human protein-protein interactions(PPIs)network,comprising 3591 human proteins interacting with 31 SARS-CoV-2 viral *** the RobustRankAggregation method,we identified 123 multiple cell line common genes(CLCGs),of which 115 up-regulated CLCGs showed host enhanced innate immunity and chemotactic response *** with network analysis,co-expression and functional enrichment analysis,we discovered four key host factors involved in SARS-CoV-2 infection:IFITM1,SERPINE1,DDX60,and ***,SERPINE1 was found to facilitate SARSCoV-2 replication,and can alleviate the endoplasmic reticulum(ER)stress induced by ORF8 protein through interaction with *** findings highlight the importance of systematic integration analysis in understanding SARS-CoV-2-human interactions and provide valuable insights for future research on potential therapeutic targets against SARS-CoV-2 infection.

关键词： SARS-CoV-2 Interactome Transcriptome Integration analysis ER stress

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Pseudovirus-based neuraminidase inhibition assays reveal potential H5N1 drug-resistant mutations

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Protein & Cell 2013年第5期4卷 356-363页

作者： Yi Lu taijiao jiang Key Laboratory of Protein and Peptide Pharmaceuticals National Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China

The use of antiviral drugs such as influenza neuraminidase (NA) inhibitors is a critical strategy to prevent and control flu pandemic, but this strategy faces the challenge of emerging drug-resistant strains. For a highly pathogenic avian influenza (HPAI) H5N1 virus, biosafety restrictions have significantly limited the efforts to monitor its drug responses and mechanisms involved. In this study, a rapid and biosafe assay based on NA pseudovirus was developed to study the resistance of HPAI H5N1 virus to NA inhibitor drugs. The H5N1 NA pseudovirus was comprehensively tested using oseltamivir-sensitive strains and their resistant mutants. Results were consistent with those in previous studies, in which live H5N1 viruses were used. Several oseltamivir-resistant mutations reported in human H1N1 were also identified to cause decreased oseltamivir sensitivity in H5N1 NA by using the H5N1 NA pseudovirus. Thus, H5N1 NA pseudoviruses could be used to monitor HPAI H5N1 drug resistance rapidly and safely.

关键词： infl uenza virus H5N1 neuraminidase inhibi-tor drug resistance pseudovirus

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Synthetic circuits, devices and modules

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Protein & Cell 2010年第11期1卷 974-978页

作者： Hong Zhang taijiao jiang National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

The aim of synthetic biology is to design artificial biological systems for novel *** an engineering perspective,construction of biological systems of defined functionality in a hierarchical way is fundamental to this emerging ***,we highlight some current advances on design of several basic building blocks in synthetic biology including the artificial gene control elements,synthetic circuits and their assemblies into devices and *** engineered basic building blocks largely expand the synthetic toolbox and contribute to our understanding of the underlying design principles of living cells.

关键词： synthetic biology genetic circuit synthetic device module

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Prediction of the Receptorome for the Human-Infecting Virome

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Virologica Sinica 2021年第1期36卷 133-140页

作者： Zheng Zhang Sifan Ye Aiping Wu taijiao jiang Yousong Peng Bioinformatics Center of College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Suzhou Institute of Systems Medicine Suzhou 215123China Guangzhou Regenerative Medicine and Health Guangdong Laboratory Guangzhou 510005China

The virus receptors are key for the viral infection of host *** of the virus receptors is still challenging at *** previous study has shown that human virus receptor proteins have some unique features including high N-glycosylation level,high number of interaction partners and high expression ***,a random-forest model was built to identify human virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human virus receptors and protein sequences.A total of 1424 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting *** addition,the combination of the random-forest model with protein–protein interactions between human and viruses predicted in previous studies enabled further prediction of the receptors for 693 human-infecting viruses,such as the enterovirus,norovirus and West Nile ***,the candidate alternative receptors of the SARS-Co V-2 were also predicted in this *** far as we know,this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the receptors for viruses.

关键词： Receptor Human-infecting virus Virome Bioinformatics Emerging virus

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Computational analysis of antigenic epitopes of avian influenza A (H7N9) viruses

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Science China(Life Sciences) 2015年第7期58卷 687-693页

作者： LIU Mi SONG TingRui HUA Sha WU AiPing jiang taijiao Institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences

Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin(HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread concern. However, evolution of the antigenicity of this virus is not well understood. Here, we inferred the antigenic epitopes of the HA protein from all H7 viruses, based on the five well-characterized HA epitopes of the human H3N2 virus. By comparing the two major H7 phylogenetic lineages, i.e., the Eurasian lineage and the North American lineage, we found that epitopes A and B are more frequently mutated in the Eurasian lineage, while epitopes B and C are more frequently mutated in the North American lineage. Furthermore, we found that the novel H7N9 virus(derived from the Eurasian lineage) isolated in China in the year 2013, contains six frequently mutated sites on epitopes that include site 135, which is located in the receptor binding domain. This indicates that the novel H7N9 virus that infects human may already have been subjected to gradual immune pressure and receptor-binding variation. Our results not only provide insights into the antigenic evolution of the H7 virus but may also help in the selection of suitable vaccine strains.

关键词：禽流感病毒抗原表位计算人类感染基因突变突变位点病毒感染病毒抗原

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Progress and Challenge in Computational Identification of Influenza Virus Reassortment

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Virologica Sinica 2021年第6期36卷 1273-1283页

作者： Xiao Ding Luyao Qin Jing Meng Yousong Peng Aiping Wu taijiao jiang Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Guangzhou 510005China Suzhou Institute of Systems Medicine SuzhouJiangsu 215123China

Genomic reassortment is an important evolutionary mechanism for influenza *** this process,the novel viruses acquire new characteristics by the exchange of the intact gene segments among multiple influenza virus genomes,which may cause flu endemics and epidemics within or even across *** to the safety and ethical limitations of the experimental studies on influenza virus reassortment,numerous computational researches on the influenza virus reassortment have been done with the explosion of the influenza virus genomic data.A great amount of computational methods and bioinformatics databases were developed to facilitate the identification of influenza virus *** this review,we summarized the progress and challenge of the bioinformatics research on influenza virus reassortment,which can guide the researchers to investigate the influenza virus reassortment events reasonably and provide valuable insight to develop the related computational identification tools.

关键词： Influenza virus Reassortment Bioinformatics Identification Database

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New targets for controlling Ebola virus disease

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National Science Review 2015年第3期2卷 266-267页

作者： F.Xiao-Feng Qin Cheng-Yu jiang taijiao jiang Genhong Cheng Center for Systems Medicine Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences Department of Biochemistry and Molecular Biology Peking Union Medical College Tsinghua University Key Laboratory of Protein and Peptide Pharmaceuticals Institute of Biophysics Chinese Academy of Sciences Department of Microbiology Immunology and Molecular Genetics University of California

EBOV infects multiple diferent cell types and replicates rapidly in vivo[1].Due to its long ilamentous structure,EBOV is internalized by macropinocytosis ater cell surface receptor binding by the viral glycoprotein(GP).Unlike many other enveloped viruses,EBOV entry process involves multiple steps of traversing of the virion through endosomal vesicle route before its nuclear core is released into cell cytoplasm for replication[2].

关键词： New targets for controlling Ebola virus disease GP TPC

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Large discrepancy between the two-way rNHT distances in hemagglutinin-inhibition assay

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Virologica Sinica 2016年第5期31卷 441-443页

作者： Yousong Peng Dayan Wang Yuelong Shu taijiao jiang College of Biology Hunan UniversityChangsha 410082China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China Center of System Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Suzhou Institute of Systems Medicine Suzhou 215123China

Dear Editor,The influenza viruses cause continual epidemics in human *** is reported by the World Health Organization(WHO),each year the seasonal influenza viruses,i.e.,human influenza A(H1N1),A(H3N2)and B viruses,inf... 详细信息

关键词： NHT Large discrepancy between the two-way rNHT distances in hemagglutinin-inhibition assay Figure

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