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PNAS文章點擊次數：2892 更新時間：2011-03-02
中國農大教授PNAS文章
www.www-991199.com來自中國農業大學醫學院，山東動物疾病控制中心等處的研究人員通過分析H1N1和H9N2流感病毒，提出雜交流感病毒可能具有大流行的潛力，這為未來流感病毒的防控提供了重要的理論參考。這一研究成果公布在《美國國家科學院院刊》（PNAS）雜志上。
文章的通訊作者是中國農大劉金華教授，*作者是動物醫學院農業部人畜共患病重點實驗室孫怡朋博士。這項成果是劉金華教授課題組于2005年在Science、2007年在Lancet等雜志發表文章以來，取得的又一項重要研究成果。
豬源H1N1/2009流感病毒自2009年爆發以來，在世界范圍迅速傳播，給人類健康造成了嚴重威脅。重排是流感病毒進化的主要方式之一，歷*多次流感的流行都是病毒重排的結果。
在這篇文章中，研究人員發現禽流感H9N2病毒與H1N1流感病毒當同時感染同一個宿主（如豬或人）的時候，很容易發生重排，且部分重排病毒的毒力明顯提高。
研究人員利用反向遺傳操作技術和小鼠模型對H1N1病毒和禽H9N2病毒的重排性開展了研究，他們獲得了127種雜交病毒，從中探討雜交病毒的致病性。結果發現，這兩種病毒極易發生重排，重排病毒容易感染小鼠且部分重排病毒較兩株親本病毒致病力明顯提高：一半以上的雜交病毒立即感染了小鼠并且復制效率和親本毒株類似，其中8種雜交病毒被證明比兩種親本毒株的毒力更強。通過對強毒力重排病毒基因組分析，研究人員發現所有強毒力病毒的PA基因均來自于H1N1流感病毒。
來自世界衛生組織的專家提出，在兩年前感染人們的H1N1大流行流感如今處于“后大流行”階段，以季節流感的形式流行。但是這些發現提示，如果發生遺傳重配，這種病毒仍然可能對公共衛生帶來重大的威脅，因此研究人員建議在流感監控中應重視新型重排病毒的產生，尤其是那些攜帶有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.
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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