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| 1 | H5N1 influenza viruses: outbreaks and biological properties显示文摘流行性感冒的所有已知的子类型 A 病毒在野水鸟被维持,这些病毒的自然水库。流行性感冒 A 病毒被孤立从许多有改变病态和死亡率的动物种类。更重要地,流行性感冒 A 病毒与潜在地致命的结果在人引起呼吸疾病。在人的本地或全球的爆发被过量住院和死亡典型地描绘。在 1997, H5N1 子类型的高度病原的鸟的流行性感冒病毒在传给人的香港出现了,导致由鸟的流行性感冒病毒感染的人的死亡的首先记录的盒子。在越南,印度尼西亚,和泰国在家禽在 2003 年 7 月开始的新爆发,和高度病原的鸟的 H5N1 流行性感冒病毒后来在整个亚洲并且进欧洲和非洲传播了。这些病毒继续与高死亡率感染人并且引起隐约可见的世界范围的担心流行。而且, H5N1 病毒爆发在整个亚洲在家禽工业上有破坏效果。因为 H5N1 病毒爆发看起来从南部的中国发源,我们这里在中国检验 H5N1 流行性感冒病毒,与他们的生物性质上的一个重音。 | Gabriele Neuman Hualan Chen George F Gao Yuelong Shu Yoshihiro Kawaoka | 2010 | Cell Research2010，20，1： | 19 |
| 2 | Lessons learnt from the human infections of avian-origin influenza A H7N9 virus:Live free markets and human health显示文摘Recent outbreak of avian-origin influenza A (H7N9) virus in the Yangtze River Delta area, China, expanding to neighboring areas in a later stage, with 36 deaths of 130 cases (as of May 16th) reminds the world of the | WU Ying George F GAO | 2013 | Science China(Life Sciences)2013，56，6： | 14 |
| 3 | A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein显示文摘最新新兴的中东呼吸症候群 coronavirus (MERS-CoV ) 能在人引起严重、致命的急性呼吸疾病。尽管有全球努力,潜力为一联系在未来流行不能被排除。有效相对的措施的发展是迫切的。MERS-CoV-specific 抗病毒的药或疫苗是还没可得到的。使用 MERS-CoV (MERS-RBD ) 的尖铁受体绑定领域使老鼠免疫,我们识别了二抵销 monoclonal 抗体(mAbs ) 4C2 和 2E6。两 mAbs potently 与高功效在 vitro 绑在 MERS-RBD 和块病毒入口。我们进一步由使在 Fab 碎片和 RBD 之间的建筑群结晶调查了他们中立化的机制,并且解决了 4C2 Fab/MERS-RBD 建筑群的结构。结构证明 4C2 认出部分重叠的 epitope 在 MERS-RBD 的受体绑定脚印,从而由位的阻碍者和接口残余竞争防碍病毒 / 受体相互作用。2E6 也堵住受体绑定,并且为绑定与 4C2 竞争到 MERS-RBD。基于结构,我们进一步由保存仅仅 paratope 残余并且从人的免疫球蛋白与对应物代替留下的氨基酸使 4C2 人性化。人性化的 4C2 (4C2h ) 抗体支撑了类似的抵销的活动和生物化学的特征到父母老鼠抗体。最后,我们证明 4C2h 能显著地在感染 MERS-CoV 的 Ad5-hCD26-transduced 鼠标的肺消除病毒 titers,因此在临床的设置为预防和治疗代表一个有希望的代理人。 | Yan Li YuhuaWan Peipei Liu Jincun Zhao Guangwen Lu Jianxun Qi Qihui Wang Xuancheng LU Ying Wu Weniun Liu Buchang Zhang Kwok-Yung Yuen Stanley Perlman George F Gao Jinghua Yan | 2015 | Cell Research2015，25，11： | 14 |
| 4 | In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009显示文摘The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza viruses.We analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes.We compared their differences and similarities systematically.Based on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor.The D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported work.This HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion function.The 2009 S-OIV HA also has an extra glycosylation site at position 276.Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation site.The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined.These results are critical for understanding the pathogenicity of the virus and host immune response against the virus. | Christopher VAVRICKA GAO George F | 2010 | Science China(Life Sciences)2010，53，6： | 11 |
| 5 | Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy显示文摘 | Kefang Liu ShuguangTan Yan Chai Danqing Chen Hao Song Catherine Wei-Hong Zhang yi Shi Jun Liu Wenjie Tan Jianxin Lyu Shah Gao Jinghua Yan Jianxun Qi George F Gao | 2017 | Cell Research2017，27，1： | 11 |
| 6 | It is not just AIV:From avian to swine-origin influenza virus显示文摘In March and early April 2009,a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States. The virus spreads worldwide by human-to-human transmission. | GAO George F | 2010 | Science China(Life Sciences)2010，53，1： | 10 |
| 7 | Structure and receptor-binding properties of an airborne transmissible avian infl uenza A virus hemagglutinin H5(VN1203mut)显示文摘Avian infl uenza A virus continues to pose a global threat with occasional H5N1 human infections,which is em-phasized by a recent severe human infection caused by avian-origin H7N9 in China.Luckily these viruses do not transmit effi ciently in human populations.With a few ami-no acid substitutions of the hemagglutinin H5 protein in the laboratory,two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model.Here in this study one of the mutant H5 proteins devel-oped by Kawaoka’s group(VN1203mut)was expressed in a baculovirus system and its receptor-binding properties were assessed.We herein show that the VN1203mut had a dramatically reduced binding affi nity for the avianα2,3-linkage receptor compared to wild type but showed no detectable increase in affi nity for the humanα2,6-linkage receptor,using Surface Plasmon Resonance techonology.Further,the crystal structures of the VN1203mut and its complexes with either human or avian receptors demon-strate that the VN1203mut binds the human receptor in the same binding manner(cis conformation)as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses.Our receptor binding and crystallo-graphic data shown here further confi rm that the ability to bind the avian receptor has to decrease for a higher hu-man receptor binding affi nity.As the Q226L substitution is shown important for obtaining human receptor binding,we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution. | Xishan Lu Yi Shi Wei Zhang Yanfang Zhang Jianxun Qi George F Gao | 2013 | Protein & Cell2013，4，7： | 9 |
| 8 | Seeing is believing:anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy显示文摘Structural immunology,focusing on structures of host immune related molecules,enables the immunologists to see what the molecules look like,and more importantly,how they work together.Antibody-based PD-1/PD-L1 blockade therapy has achieved brilliant successes in clinical applications.The recent breakthrough of the complex structures of checkpoint blockade antibodies with their counterparts,pembrolizumab with PD-1 and avelumab with PD-L1,have made it clear how these monoclonal antibodies compete the binding of PD-1/PD-L1 and function to blockade the receptor-ligand interaction.Herein,we summarize the structural findings of these two reports and look into the future for how this information would facilitate the development of more efficient PD-1/PD-L1 targeting antibodies,small molecule drugs,and other protein or non-protein inhibitors. | Shuguang Tan Catherine W-H Zhang George F Gao | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 8 |
| 9 | CD8:Adhesion Molecule,Co-Receptor and Immuno-Modulator显示文摘CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes, which are important components in cellular immunity, esp. In the immune response to cancer and chronic infections. There are two forms of CD8,either as an αα homodimer or αβ heterodimer. It acts as an 'assistant' or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor (αβTCR) and its ligand peptide major histocompatibility complex (pMHC). CD8 also binds to pMHC but away from the interface of pMHC and TCR contact, thereof no influence on the specificity of this interaction. If the TCR and CD8 bind to the same pMHC at the same time, CD8 is defined as a co-receptor, functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway; if CD8 binds to pMHC independently of the TCR, it is defined as an adhesion molecule. At present, the co-receptor function theory is dominated in the field.Recent study has also shown that murine CD8αα binds to TL antigen, an MHC homologue, therefore acts as an immuno-modulator. In this review, we discuss these current understandings of the three aspects of the CD8 functions and their structural basis. | David K Cole George F Gao | 2004 | Cellular & Molecular Immunology2004，1，2： | 4 |
| 10 | Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010显示文摘 | Gonghuan Yang Yu Wang Yixin Zeng George F Gao Xiaofeng Liang Maigeng Zhou Xia Wan Shicheng Yu Yuhong Jiang Mohsen Naghavi Theo Vos Haidong Wang Alan D Lopez Christopher JL Murray | 2013 | The Lancet . 2013 (9882)2013，，9882： | 4 |
| 11 | An octamer of enolase from Streptococcus suis显示文摘Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic cells.The enzyme can also locate on the cell surface and bind to plasminogen,via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host cells.The functions of the eukaryotic enzymes on the cell surface expression(including T cells,B cells,neutrophils,monocytoes,neuronal cells and epithelial cells)are not known.Streptococcus suis serotype 2(S.suis 2,SS2)is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome(STSS)never seen before in human sufferers.We recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal S.suis 2 infection.In this study,a 2.4-angstrom structure of the SS2 enolase is solved,revealing an octameric arrangement in the crystal.We further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation assay.These results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as well.This is,to our knowledge,the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically,and the second octamer enolase structure in addition to that of Streptococcus pneumoniae.We also investigated the plasminogen binding property of the SS2 enzyme. | Qiong Lu Hao Lu Jianxun Qi Guangwen Lu George F Gao | 2012 | Protein & Cell2012，3，10： | 4 |
| 12 | Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010显示文摘 | Gonghuan Yang Yu Wang Yixin Zeng George F Gao Xiaofeng Liang Maigeng Zhou Xia Wan Shicheng Yu Yuhong Jiang Mohsen Naghavi Theo Vos Haidong Wang Alan D Lopez Christopher JL Murray | 2013 | The Lancet2013，，9882： | 3 |
| 13 | Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010显示文摘 | Gonghuan Yang Yu Wang Yixin Zeng George F Gao Xiaofeng Liang Maigeng Zhou Xia Wan Shicheng Yu Yuhong Jiang Mohsen Naghavi Theo Vos Haidong Wang Alan D Lopez Christopher JL Murray | 2013 | 2013 (9882)2013，，9882： | 3 |
| 14 | An mRNA-based vaccine strategy against Zika显示文摘 | Gary Wong George F Gao | 2017 | Cell Research2017，27，9： | 3 |
| 15 | Development of a reverse transcription quantitative polymerase chain reaction-based assay for broad coverage detection of African and Asian Zika virus lineages显示文摘The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions. | Yang Yang Gary Wong Baoguo Ye Shihua Li Shanqin Li Haixia Zheng Qiang Wang Mifang Liang George F Gao Lei Liu Yingxia Liu Yuhai Bi | 2017 | Virologica Sinica2017，32，3： | 3 |
| 16 | Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses显示文摘 | Di Liu Weifeng Shi Yi Shi Dayan Wang Haixia Xiao Wei Li Yuhai Bi Ying Wu Xianbin Li Jinghua Yan Wenjun Liu Guoping Zhao Weizhong Yang Yu Wang Juncai Ma Yuelong Shu Fumin Lei George F Gao | 2013 | The Lancet2013，，9881： | 2 |
| 17 | Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses显示文摘 | Di Liu Weifeng Shi Yi Shi Dayan Wang Haixia Xiao Wei Li Yuhai Bi Ying Wu Xianbin Li Jinghua Yan Wenjun Liu Guoping Zhao Weizhong Yang Yu Wang Juncai Ma Yuelong Shu Fumin Lei George F Gao | 2013 | The Lancet2013，，9881： | 1 |
| 18 | Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010显示文摘 | Gonghuan Yang Yu Wang Yixin Zeng George F Gao Xiaofeng Liang Maigeng Zhou Xia Wan Shicheng Yu Yuhong Jiang Mohsen Naghavi Theo Vos Haidong Wang Alan D Lopez Christopher JL Murray | 2013 | The Lancet2013，，9882： | 1 |
| 19 | Emergence of fatal PRRSV variants:unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark显示文摘 | KEGONG TIAN GEORGE F GAO | 2007 | Plosone2007，2，6： | 1 |
| 20 | Poultry carrying HgN2 act as incubators for novel human avian influ- enza viruses显示文摘 | Di Liu Weifeng Shi George F Gao | 2014 | The Lancet2014，384，： | 1 |
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