简介：Thesurfaceglycoproteinhemagglutinin(HA)helpstheinfluenzaAvirustoevadethehostimmunesystembyantigenicvariationandisamajordrivingforceforviralevolution.Inthisstudy,theselectionpressureonHAofH5N1influenzaAviruswasanalyzedusingbioinformaticsalgorithms.Mostoftheidentifiedpositiveselection(PS)siteswerefoundtobewithinoradjacenttoepitopesites.SomeoftheidentifiedPSsitesareconsistentwithpreviousexperimentalstudies,providingfurthersupporttothebiologicalsignificanceofourfindings.ThehighestfrequencyofPSsiteswasobservedinrecentstrainsisolatedduring2005–2007.PhylogeneticanalysiswasalsoconductedonHAsequencesfromvarioushosts.Viraldriftisalmostsimilarinbothavianandhumanspecieswithaprogressivetrendovertheyears.OurstudyreportsnewmutationsinfunctionalregionsofHAthatmightprovidemarkersforvaccinedesignorcanbeusedtopredictisolatesofpandemicpotential.

简介：AbstractBackground:The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.Methods:H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.Results:The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.Conclusion:The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

简介：高度病原的鸟的流行性感冒H5N1流行病是重要公共健康危险。有哺乳动物的传播活动的遗传上设计的H5N1病毒加亮人的流行性感冒H5N1的潜在的风险流行。响应流行性感冒H5N1病毒理解天生的免疫系统的内在的原则将导致这些潜在地致命的病毒的改进预防和控制。γ；δ；当第一对微生物引起的感染防卫排队并且帮助在病毒的感染的早阶段期间开始适应有免疫力的回答，T房间行动。在这研究，我们调查了γ的分子的机制；δ；响应流行性感冒H5N1病毒的感染的T房间。我们发现从流行性感冒H5N1病毒的三不同紧张导出的recombinant红血球凝聚素(rHA)得到了γ的激活；δ；在外部血mononuclear房间(PBMC)有教养的T房间。两CD69的房间表面表示，γ上的一个早激活标记；δ；interferon-γ的T房间，和生产；(IFN-γ；)显著地被增加。尤其是，rHA导致蛋白质的γ；δ；T房间激活没被TCRγ调停；δ；，NKG2D或模式识别受体(PRR)或NKp46受体。有sialic酸受体的rHA蛋白质的相互作用可以在γ起一个关键作用；δ；T房间激活。我们的数据可以提供卓见进位于γ下面的机制；δ；响应有H5N1病毒的感染的T房间激活。

简介：流行性感冒病毒红血球凝聚素的梗区域很好相对与球状的头领域相比被保存，它对流行性感冒用作一支通用疫苗使它成为一个潜在的目标。然而，在红血球凝聚素的CD4T房间的角色梗特定的有免疫力的反应不是清楚的。这里，我们识别了在流行性感冒的尚不致命的感染以后从红血球凝聚素梗领域包含残余HA2113-131的老鼠CD4T房间epitope。响应有识别epitope的刺激，从感染的老鼠导出的splenocytes显示出象degranulation一样由IL-2，TNF-和IFN-生产出现的重要polyfunctionality。而且，与相应于这CD4T房间epitope的肽使免疫的老鼠展出了CD4T房间受体分享的interindividual序列，和他们有更高的幸存率与流行H1N1流行性感冒的致命的剂量跟随挑战病毒。因此，我们的数据表明了红血球凝聚素的一个关键角色在对流行性感冒病毒感染的主机免疫者反应的梗特定的CD4T房间。