The hemagglutinin (HA) of influenza viruses in itiates virus infection by binding receptors on host cells. Human influenza viruses preferenti ally bind to receptors with α2,6 linkages to gala ctose, avian viruses pre...The hemagglutinin (HA) of influenza viruses in itiates virus infection by binding receptors on host cells. Human influenza viruses preferenti ally bind to receptors with α2,6 linkages to gala ctose, avian viruses prefer receptors with α2,3 linkages to galactose, and swine viruses favor both types of receptors. The pandemic H1N1 2009 remains a global health concern in 2010. The novel 2009 H1N1 influenza virus has its ge netic components from avian, human, and sw ine viruses. Its pandemic nature is characterized clearly by its dual binding to the α2,3 as well as α2,6 receptors, because the seasonal human H1N1 virus only binds to the α2,6 receptor. In pr evious studies, the informational spectrum me thod (ISM), a bioinformatics method, was appli ed to uncover highly conserved regions in the HA protein associated with the primary receptor binding preference in various subtypes. In the present study, we extended the previous work by discovering multiple domains in HA associa ted with the secondary receptor binding prefer ence in various subtypes, thus characterizing the distinct dual binding nature of these viruses. The domains discovered in the HA proteins were mapped to the 3D homology model of HA, which could be utilized as therapeutic and diag nostic targets for the prevention and treatment of influenza infection.展开更多
Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly de...Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly demonstrated that only five mutations, fewer than previously estimated, are needed to make avian H5N1 influenza transmissible between ferrets through the air, raising fears that a human pandemic is possible if this virus escapes from the lab. Of the five mutations found, four of them are located in the HA gene that is responsible for the viral entry into the host cells. A crucial step for avian influenza to go across the species boundary to infect humans is the switch of its receptor binding specificity from avian to human types. The first task of this study was to quantify the individual as well as the collective effect of the known HA mutations from the previous research on receptor binding selection. Our second task was to identify new combinations of HA mutations that could change the receptor binding preference of H5N1 from avian to human types. Our findings thus deepened our understanding of the previous research and also extended its results by discovering new combinations of mutations that could enhance the binding of avian H5N1 to human type receptors while reduce that to avian types.展开更多
Traditionally, the multibasic cleavage site （MBCS） of surface protein H5-hemagglutinin （HA） is converted to a monobasic one so as to weaken the virulence of recombinant H5N1 influenza viruses and to produce inacti...Traditionally, the multibasic cleavage site （MBCS） of surface protein H5-hemagglutinin （HA） is converted to a monobasic one so as to weaken the virulence of recombinant H5N1 influenza viruses and to produce inactivated and live attenuated vaccines. Whether such modification benefits new candidate vaccines has not been adequately investigated. We previously used retroviral vectors to generate wtH5N1 pseudotypes containing the wild-type HA （wtH5） from A/swine/Anhui/ca/2004 （H5N1） virus. Here, we generated mtH5N1 pseudotypes, which contained a mutant-type HA （mtH5） with a modified monobasic cleavage site. Groups of mice were subcutaneously injected with the two types of influenza pseudotypes. Compared to the group immunized with wtH5N1 pseudotypes, the inoculation of mtH5N1 pseudotypes induced significantly higher levels of HA specific IgG and IFN-y in immunized mice, and enhanced protection against the challenge of mouse-adapted avian influenza virus A/Chicken/Henardl2/2004 （H5N1）. This study suggests modification of the H5-hemagglutinin MBCS in retroviral pseudotypes enhances protection efficacy in mice and this information may be helpful for development of vaccines from mammalian cells to fight against H5N 1 influenza viruses.展开更多
目的探讨富血小板血浆(PRP)联合透明质酸(HA)关节内注射与PRP单独注射相比的疗效和安全性,为膝骨性关节炎(KOA)的治疗提供循证策略。方法查阅PubMed、Web of Science、中国知网(CNKI)、万方数据库,检索建库初到2021年10月公开发表的文...目的探讨富血小板血浆(PRP)联合透明质酸(HA)关节内注射与PRP单独注射相比的疗效和安全性,为膝骨性关节炎(KOA)的治疗提供循证策略。方法查阅PubMed、Web of Science、中国知网(CNKI)、万方数据库,检索建库初到2021年10月公开发表的文献。纳入已发表的随机对照实验(RCT)或队列研究。研究对象为KOA患者,实验组为PRP联合HA关节内注射,对照组为PRP或HA关节内注射。对纳入RCT研究使用Cochrane手册风险评估工具进行质量评价,队列研究使用Newcastle-Ottawa Scale进行质量评价,用RevMan5.3软件对结局指标进行Meta分析。结果纳入10篇文献,共1110例患者,其中PRP组467例,PRP+HA组450例,HA组193例。Meta分析结果显示,PRP+HA组在治疗6个月后视觉模拟评分(VAS,MD:-0.31;95%CI(-0.60~-0.03);P=0.03)、西大略和麦克马斯特大学骨关节炎指数(WOMAC)评分(MD:-2.81;95%CI(-4.48~-1.13);P=0.001)、Lequesne指数(MD:-1.46;95%CI(-2.01~-0.90);P<0.00001)均显著优于PRP组;两组并发症发生率无统计学意义(RD:0.00;95%CI(-0.03~0.04);P=0.97)。结论PRP联合HA治疗KOA具有良好的临床治疗效果。基于此Meta分析,与单纯关节内注射PRP相比,PRP联合HA可提高治疗6个月后的WOMAC评分、VAS评分和Lequesne指数评分。在并发症发生率方面,两种治疗方案的安全性相似。展开更多
文摘The hemagglutinin (HA) of influenza viruses in itiates virus infection by binding receptors on host cells. Human influenza viruses preferenti ally bind to receptors with α2,6 linkages to gala ctose, avian viruses prefer receptors with α2,3 linkages to galactose, and swine viruses favor both types of receptors. The pandemic H1N1 2009 remains a global health concern in 2010. The novel 2009 H1N1 influenza virus has its ge netic components from avian, human, and sw ine viruses. Its pandemic nature is characterized clearly by its dual binding to the α2,3 as well as α2,6 receptors, because the seasonal human H1N1 virus only binds to the α2,6 receptor. In pr evious studies, the informational spectrum me thod (ISM), a bioinformatics method, was appli ed to uncover highly conserved regions in the HA protein associated with the primary receptor binding preference in various subtypes. In the present study, we extended the previous work by discovering multiple domains in HA associa ted with the secondary receptor binding prefer ence in various subtypes, thus characterizing the distinct dual binding nature of these viruses. The domains discovered in the HA proteins were mapped to the 3D homology model of HA, which could be utilized as therapeutic and diag nostic targets for the prevention and treatment of influenza infection.
文摘Researchers have been searching for molecular features that could make avian H5N1 influenza transmissible among people since the first report of human infections with this virus in 1997. A recent study surprisingly demonstrated that only five mutations, fewer than previously estimated, are needed to make avian H5N1 influenza transmissible between ferrets through the air, raising fears that a human pandemic is possible if this virus escapes from the lab. Of the five mutations found, four of them are located in the HA gene that is responsible for the viral entry into the host cells. A crucial step for avian influenza to go across the species boundary to infect humans is the switch of its receptor binding specificity from avian to human types. The first task of this study was to quantify the individual as well as the collective effect of the known HA mutations from the previous research on receptor binding selection. Our second task was to identify new combinations of HA mutations that could change the receptor binding preference of H5N1 from avian to human types. Our findings thus deepened our understanding of the previous research and also extended its results by discovering new combinations of mutations that could enhance the binding of avian H5N1 to human type receptors while reduce that to avian types.
基金supported by the National Basic Research Program of China (973: 2012CB518904) from the Ministry of Science and Technology of Chinathe National Natural Science Foundation of China(81201298)
文摘Traditionally, the multibasic cleavage site （MBCS） of surface protein H5-hemagglutinin （HA） is converted to a monobasic one so as to weaken the virulence of recombinant H5N1 influenza viruses and to produce inactivated and live attenuated vaccines. Whether such modification benefits new candidate vaccines has not been adequately investigated. We previously used retroviral vectors to generate wtH5N1 pseudotypes containing the wild-type HA （wtH5） from A/swine/Anhui/ca/2004 （H5N1） virus. Here, we generated mtH5N1 pseudotypes, which contained a mutant-type HA （mtH5） with a modified monobasic cleavage site. Groups of mice were subcutaneously injected with the two types of influenza pseudotypes. Compared to the group immunized with wtH5N1 pseudotypes, the inoculation of mtH5N1 pseudotypes induced significantly higher levels of HA specific IgG and IFN-y in immunized mice, and enhanced protection against the challenge of mouse-adapted avian influenza virus A/Chicken/Henardl2/2004 （H5N1）. This study suggests modification of the H5-hemagglutinin MBCS in retroviral pseudotypes enhances protection efficacy in mice and this information may be helpful for development of vaccines from mammalian cells to fight against H5N 1 influenza viruses.
文摘目的探讨富血小板血浆(PRP)联合透明质酸(HA)关节内注射与PRP单独注射相比的疗效和安全性,为膝骨性关节炎(KOA)的治疗提供循证策略。方法查阅PubMed、Web of Science、中国知网(CNKI)、万方数据库,检索建库初到2021年10月公开发表的文献。纳入已发表的随机对照实验(RCT)或队列研究。研究对象为KOA患者,实验组为PRP联合HA关节内注射,对照组为PRP或HA关节内注射。对纳入RCT研究使用Cochrane手册风险评估工具进行质量评价,队列研究使用Newcastle-Ottawa Scale进行质量评价,用RevMan5.3软件对结局指标进行Meta分析。结果纳入10篇文献,共1110例患者,其中PRP组467例,PRP+HA组450例,HA组193例。Meta分析结果显示,PRP+HA组在治疗6个月后视觉模拟评分(VAS,MD:-0.31;95%CI(-0.60~-0.03);P=0.03)、西大略和麦克马斯特大学骨关节炎指数(WOMAC)评分(MD:-2.81;95%CI(-4.48~-1.13);P=0.001)、Lequesne指数(MD:-1.46;95%CI(-2.01~-0.90);P<0.00001)均显著优于PRP组;两组并发症发生率无统计学意义(RD:0.00;95%CI(-0.03~0.04);P=0.97)。结论PRP联合HA治疗KOA具有良好的临床治疗效果。基于此Meta分析,与单纯关节内注射PRP相比,PRP联合HA可提高治疗6个月后的WOMAC评分、VAS评分和Lequesne指数评分。在并发症发生率方面,两种治疗方案的安全性相似。
