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Can Ebola virus become endemic in the human population？

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Protein & Cell 2016年第1期7卷 4-6页

作者： Gary Wong george f. gao Xiangguo Qiu Special Pathogens Program National Microbiology Laboratory Public Health Agency of Canada Winnipeg MB CanadaDepartment of Medical Microbiology University of Manitoba Winnipeg MB Canada Department of.Medical Microbiology University of Manitoba Winnipeg MB Canada CAS Key Laboratory of.Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of SciencesBeijing 100101 China National Institute f.r Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100052 China Of.iceof.Director-General Chinese Center for Disease Control and Prevention Beijing 102206 China

The 2014-15 Ebola virus reported during March 2014 Guinea. has shown itself.to （EBOV） outbreak, originally n the Western Af.ican nation of.be resistant to traditional con- tainment methods, with over 28,000 inf.ctions and 11,000 deaths over 18 months. Recently, news that a Scottish nurse had relapsed to EBOV disease with neurological symptoms at 10 months af.er recovery have astonished experts. The prolonged nature of.the outbreak has led to questions whether EBOV can become endemic in the human popula- tion, an undesirable outcome due to the large amount of.resources required to keep this virus under control. In this commentary, we discuss aspects EBOV disease with those caused by pathogens considered endemic in humans, as well as f.ctors which may contribute to sustained EBOV transmission in humans.

关键词： High Case f.tality Rate EBOV Inf.ction Severe Hemorrhagic f.ver Minor Public Health EBOV Outbreak

An inf.ctious clone of.the highly pathogenic porcine reproductive and respiratory syndrome virus: Topology of.glycoprotein 3 (GP3) addressing the intrachain disulf.de bonds

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Chinese Science Bulletin 2011年第26期56卷 2785-2793页

作者： f.NG ChunYan LIU YueHuan YAN JingHua george f. gao CAS Key Laboratory of.Pathogenic Microbiology and Immunology (CASPMI) Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China Graduate University of.Chinese Academy of.Sciences Beijing 100049 China Institute of.Animal Husbandry and Veterinary Medicine Beijing Academy of Agriculture and Forestry Sciences Beijing 100097 China Beif.ng Institutes of.Lif. Science Chinese Academy of Sciences Beijing 100101 China

The highly pathogenic porcine reproductive and respiratory virus (hpPRRSV) with discontinuous 30 amino acid (aa) deletion as a gene marker has caused great economic loss in pig industry and since 2007 has become the dominant strain prevalent in China and Vietnam since *** genetics method is a powerf.l tool urgently needed to be used on the hpPRRSV to study the intriguing molecular mechanism of.transcription,replication and the virulence determinant *** our study,we successf.lly constructed a f.lllength inf.ctious clone,prBJSY07,based on hpPRRSV isolate,*** rescued virus,vrBJSY07,showed similar growth characters to those of.the parental virus,*** also f.und that a rescued virus vBJSY07 generated f.om pBJSY07 was viable but displayed decreased and delayed reproductive capacity,which might be caused by two amino acids mutations,S83C and S117C in glycoprotein 3 (GP3),acquired during the preparation of.the inf.ctious *** topology of.the wild type GP3 and the mutant were f.rther analyzed by bioinf.rmatics and revealed that the mutated GP3 possessed slightly altered structure,most likely by f.rming a new disulf.de bond between the two new cysteine *** GP3 is a cysteine-rich glycoprotein,common f.r viral glycoproteins,our results show that GP3 can accommodate even more cysteine *** on this,a topological model of.GP3 is proposed by addressing the intrachain disulf.des.

关键词：猪繁殖与呼吸综合征病毒病毒糖蛋白感染性克隆拓扑结构高致病性二硫键半胱氨酸残基链

Gluconate 5-dehydrogenase （Ga5DH） participates in Streptococcus suis cell division

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Protein & Cell 2014年第10期5卷 761-769页

作者： Zhongyu Shi Chunling Xuan Huiming Han Xia Cheng Jundong Wang Youjun f.ng Swaminath Srinivass Guangwen Lu george f. gao CAS Key Laboratory of.Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of SciencesBeijing 100101 China University of.Chinese Academy of.Sciences Beijing 100049 China College of.Animal Science and Technology Shanxi Agricultural University Taigu 030801 China Department of.Microbiology University of Illinois Urbana IL 61801 USA Department of.Biochemistry University of Illinois Urbana IL 6180 USA Laboratory of.Protein Engineering and Vaccines Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308 China Research Network of.Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101 China

Bacterial cell division is strictly regulated in the f.rmation of.equal daughter cells. This process is governed by a series of.spatial and temporal regulators, and several new f.ctors of.interest to the f.eld have recently been identif.ed. Here, we report the requirement of.gluconate 5-dehydrogenase （Ga5DH） in cell division of.the zoonotic pathogen Strepto- coccus suis. GaSDH catalyzes the reversible reduction of.5-ketogluconate to D-gluconate and was localized to the site of.cell division. The deletion of.Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A signif.cant increase was also observed in cell length. These def.cts were determined to be the conse- quence of.Ga5DH deprivation in S. suis causing f.sZ delo- calization. In addition, the interaction of.f.sZ with Ga5DH in vitro was conf.rmed by protein interaction assays. These results indicate that GaSDH may f.nction to prevent the f.rmation of.ectopic Z rings during S. suis cell division.

关键词： Streptococcus suis Ga5DH cell shape,cell division f.sZ localization

Competitive virus and host RNAs： the interplay of.a hidden virus and host interaction

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Protein & Cell 2014年第5期5卷 348-356页

作者： Changf.i Li Jun Hu Junli Hao Bao Zhao Bo Wu Lu Sun Shanxin Peng george f. gao Songdong Meng CAS Key Laboratory of.Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences(CAS) Beijing 100101 China

During virus inf.ction, viral RNAs and mRNAs f.nction as blueprints f.r viral protein synthesis and possibly as pathogen-associated molecular patterns （PAMPs） in innate immunity. Here, considering recent research progress in microRNAs （miRNAs） and competitive endogenous RNAs （ceRNAs）, we speculate that viral RNAs act as sponges and can sequester endogenous miRNAs within inf.cted cells, thus cross-regulating the stability and translational ef.iciency of.host mRNAs with shared miRNA response elements. This cross-talk and these reciprocal interactions between viral RNAs and host mRNAs are termed ＂competitive viral and host RNAs＂（cvhRNAs）. We f.rther provide recent experimental evidence f.r the existence of.cvhRNAs networks in hepatitis B virus （HBV）, as well as Her- pesvirus saimiri （HVS）, lytic murine cytomegalovirus （MCMV） and human cytomegalovirus （HCMV） inf.c- tions. In addition, the cvhRNA hypothesis also pre- dicts possible cross-regulation between host and other viruses, such as hepatitis C virus （HCV）, HIV, inf.uenza virus, human papillomaviruses （HPV）. Since the interaction between miRNAs and viral RNAs also inevitably leads to repression of.viral RNA f.nction, we speculate that virus may evolve either to employ cvhRNA networks or to avoid miRNA targeting f.r optimal f.tness within the host. CvhRNA networks may theref.re play a f.ndamental role in the regulation of.viral replication, inf.ction establishment, and viral pathogenesis.

关键词： cvhRNAs virus RNAs host mRNAs,miRNA response element ceRNAs

Crystal clear： visualizing the intervention mechanism of.the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies

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Protein & Cell 2016年第12期7卷 866-877页

作者： ShuguangTan Danqing Chen Kef.ng Liu Mengnan He Hao Song Yi Shi Jun Liu Catherine W.-H. Zhang Jianxun Qi Jinghua Yan Shan gao george f. gao CAS Key Laboratory of.Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China National Institute f.r Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention (China CDC) Beijing 102206 China College of.Laboratory Medicine and Lif. Sciences Wenzhou Medical University Wenzhou 325035 China College of.Lif. Sciences University of Chinese Academy of Sciences Beijing 100049 China Research Network of.Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of Sciences Beijing 100101 China Immuf.cell Biotechnology Co.Ltd. Beijing 100102 China CAS Key Laboratory of.Microbial Physiological and Metabolic Engineering Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China CAS Key Laboratory of.Bio-medical Diagnostics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou Jiangsu 215163 China Savaid Medical School University of Chinese Academy of Sciences Beijing 100049 China

Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies f.r cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysf.nction. In contrast to prior approaches to generate or boost tumor-specif.c T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell def.cts and restores pre- existing T-cell f.nction to modulate antitumor immunity. in this review, the f.ndamental knowledge on the expression regulations and inhibitory f.nctions of.PD-1 and the present understanding of.antibody-based PD-1/ PD-L1 blockade therapies are brief.y summarized. We then f.cus on the recent breakthrough work concerning the structural basis of.the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of.PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural inf.rmationwill benef.t the design and improvement of.therapeutic antibodies targeting PD-1 signaling.

关键词： PD-1/PD-L1 interaction checkpointblockade molecular basis therapeutic antibody

Characterization of.human αβTCR repertoire and discovery of.D-D f.sion in TCRβ chains

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Protein & Cell 2014年第8期5卷 603-615页

作者： Peipei Liu Di Liu Xi Yang Jing gaoai Ma3, f.ngqing Zhaos, Xuyu Zhou~'2~, george f. gao1'2'4'5~, Baoli Zhu~'2~ Yan Chen Xue Xiao f.i Liu Jing Zou Jun Wu Juncai Ma f.ngqing Zhao Xuyu Zhou george f. gao Baoli Zhu CAS Key Laboratory of.Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China University of.Chinese Academy of.Sciences Beijing 100049 China Network Inf.rmation Center Institute of Microbioiogy Chinese Academy of Sciences Beijing 100101 China Chinese Center f.r Disease Control and Prevention (China CDC) Beijing 102206 China Research Network of.Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101 China

The characterization of.the human T-cell receptor （TCR） repertoire has made remarkable progress, with most of.the work f.cusing on the TCRβ chains. Here, we ana- lyzed the diversity and complexity of.both the TCRa and TCRβ repertoires of.three healthy donors. We f.und that the diversity of.the TCRα repertoire is higher than that of.the TCRβ repertoire, whereas the usages of.the V and J genes tended to be pref.rential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly pref.rential. We also f.und that the TRDV1 gene rearranges with the majority of.TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene （TRAV42/DV1）. Moreover, we uncovered the presence of.tandem TRBD （TRB D gene） usage in -2% of.the productive human TCRβ CDR3 sequences.

关键词： TCR repertoire next-generationsequencing V/J usage V-J pairing CDR3 D-D f.sion

Transcontinental Translational Medicine Collaboration: A Successf.l SinoCuban Joint B-to-B Program

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Biomedical and Environmental Sciences 2013年第7期26卷 517-519页

作者： LU Kai CHEN Tao CHEN Yu george f. gao Chinese Center f.r Disease Control and Prevention

Translational medicine is a comprehensive discipline that aims to convert laboratory research results into products and technology f.r clinical application using modern molecular biological techniques, to improve our understanding of.the human body and disease and to optimize laboratory design f.r clinical observation and analysis f.r basic research. Its ultimate goal is improving holistic medicine and helping patients solve their health problems. Translational medicine includes two processes： bench to bedside and bedside to bench, known as B-to-B processes. The f.rst B-to-B （bench to bedside） ref.rs to the application of.results of.the laboratory to clinical use as a medical product or a diagnosis and treatment technology. The second B-to-B （bedside to bench） describes the process by which clinical observation and analysis provides ideas and guidance f.r experiment design f.r basic medical research. The two processes complement each other and constitute the two-way cycle of.translational medicine. Translational medicine can be applied to clinical disease detection in the f.rm of.new biomarkers and can accelerate drug discovery. In recent years, with the biotechnology, increasing rapid development of.outcomes of.research on molecular pathogenesis can be directly applied to clinical theraDv.

关键词： Transcontinental Translational Medicine Collaboration A Successf.l SinoCuban Joint B-to-B Program

A new unconventional HLA-A2-restricted epitope f.om HBV core protein elicits antiviral cytotoxic T lymphocytes

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Protein & Cell 2014年第4期5卷 317-327页

作者： Lu Sun Yu Zhang Bao Zhao Mengmeng Deng Jun Liu Xin Li Junwei Hou Mingming Gui Shuijun Zhang Xiaodong Li george f. gao Songdong Meng CAS Key Laboratory of.Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences_ (CAS) Beijing 100101 China Beijing Institute of.Inf.ctious Diseases Beijing 302 Hospital Beijing 100039 China Xinjiang Agricultural University Urumqi 830052 China

Cytotoxic T cells （CTLs） play a key role in the control of.Hepatitis B virus （HBV） inf.ction and viral clearance. However, most of.identif.ed CTL epitopes are derived f.om HBV of.genotypes A and D, and f.w have been def.ned in virus of.genotypes B and C which are more prevalent in Asia. As HBV core protein （HBc） is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool cov- ering HBc to screen and identif. specif.c CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141- 149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti- HBV activity were f.rther determined in HBV and HLA- A2 transgenic mice. f.nally, we show that mutations in HBc141-149 epitope are associated with viral parame- ters and disease progression in HBV inf.cted patients. Our data theref.re provide insights into the structure characteristics of.this unconventional epitope binding to MHC-I molecules, as well as epitope specif.c CTL activity that orchestrate T cell response and immune evasion in HBV inf.cted patients.

关键词： chronic hepatitis B HLA-A2 HBc peptideCTL response antiviral cytotoxity

Crystal Structure of.Chicken MHC class I molecule Bf.*0401 Sheds the Lights on the sensitivity def.nition to Marek's disease by the peptide binding groove

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Crystal Structure of Chicken MHC class I molecule BF2*0401 S...