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PNAS文章点击次数:1527 发布时间:2011-03-02

                               中国农大教授PNAS文章

       www.runwelltac.com来自中国农业大学医学院,山东动物疾病控制中心等处的研究人员通过分析H1N1和H9N2流感病毒,提出杂交流感病毒可能具有大流行的潜力,这为未来流感病毒的防控提供了重要的理论参考。这一研究成果公布在《美国国家科学院院刊》(PNAS)杂志上。

       文章的通讯作者是中国农大刘金华教授,*作者是动物医学院农业部人畜共患病重点实验室孙怡朋博士。这项成果是刘金华教授课题组于2005年在Science、2007年在Lancet等国际杂志发表文章以来,取得的又一项重要研究成果。

       猪源H1N1/2009流感病毒自2009年爆发以来,在世界范围迅速传播,给人类健康造成了严重威胁。重排是流感病毒进化的主要方式之一,历史上多次流感的流行都是病毒重排的结果。
在这篇文章中,研究人员发现禽流感H9N2病毒与H1N1流感病毒当同时感染同一个宿主(如猪或人)的时候,很容易发生重排,且部分重排病毒的毒力明显提高。
       研究人员利用反向遗传操作技术和小鼠模型对H1N1病毒和禽H9N2病毒的重排性开展了研究,他们获得了127种杂交病毒,从中探讨杂交病毒的致病性。结果发现,这两种病毒极易发生重排,重排病毒容易感染小鼠且部分重排病毒较两株亲本病毒致病力明显提高:一半以上的杂交病毒立即感染了小鼠并且复制效率和亲本毒株类似,其中8种杂交病毒被证明比两种亲本毒株的毒力更强。通过对强毒力重排病毒基因组分析,研究人员发现所有强毒力病毒的PA基因均来自于H1N1流感病毒。
       来自世界卫生组织的专家提出,在两年前感染人们的H1N1大流行流感如今处于“后大流行”阶段,以季节流感的形式流行。但是这些发现提示,如果发生遗传重配,这种病毒仍然可能对公共卫生带来重大的威胁,因此研究人员建议在流感监控中应重视新型重排病毒的产生,尤其是那些携带有H1N1源PA基因的重排病毒。

 

原文摘要:
High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses

H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort. To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice. These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses. All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk. Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity. Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.

 

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