High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses
High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses
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DOI：
10.1073/pnas.1019109108
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发表时间：
2011-03-08
影响因子：
11.1
通讯作者：
Liu, Jinhua
中科院分区：
文献类型：
--
作者：
Sun, Yipeng;Qin, Kun;Liu, Jinhua
H9N2流感病毒已在全球多种鸟类中传播，并反复感染包括猪和人类在内的哺乳动物，对公众健康构成重大威胁。 H9N2 病毒和 H1N1/2009 流感病毒在猪和人类中的共存为这些病毒提供了重新组合的机会。为了评估源自这些病毒的重配病毒的潜在公共风险，我们使用反向遗传学产生了127个源自禽类H9N2和大流行性H1N1病毒的H9重配病毒，并评估了它们在小鼠中的相容性、复制能力和毒力。这些杂交病毒表现出高度的遗传相容性，并且一半以上在体外复制到高滴度。对 127 个重配病毒中的 73 个进行的体内研究表明，所有病毒都能够在没有事先适应的情况下感染小鼠，并且 8 个重配病毒表现出比两种亲本病毒更高的致病性。所有毒力高于亲本病毒的重配病毒均含有2009年大流行病毒的PA基因，揭示了H1N1/2009病毒的PA基因在产生具有高公共卫生风险的重配病毒中的重要作用。对 16 种核糖核蛋白组合的聚合酶活性的体外分析表明，H1N1/2009 来源的 PA 也增强了聚合酶活性。我们的研究结果表明，一些禽类 H9 大流行性重配病毒可能会对人类造成更高的潜在威胁，同时也强调了监测可能出现的 H9 大流行重配病毒的重要性，特别是那些具有 H1N1/2009 起源的 PA 基因的病毒。
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.