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禽病室课题组在H9N2亚型AIV跨物种感染哺乳动物研究领域取得新进展

来源:禽病研究室 发布时间:2020-07-28 11:14:47

     近期,国际学术期刊Viruses刊载了山东省农业科学院畜牧兽医研究所禽病室许传田研究员课题组发表的题为“A Well-Defined H9N2 Avian Influenza Virus Genotype with High Adaption in Mammals was Prevalent in Chinese Poultry Between 2016 to 2019”的研究论文,该研究以BALB/c雌鼠为模型,评价了2016-2019年间山东及周边地区H9N2亚型AIV对哺乳动物的感染性,并进一步分析了分离株的病毒基因组进化和变异趋势,阐明其对哺乳动物生物表型的相关基因型。

  H9N2亚型AIV属于LPAIV,广泛存在重组变异现象,在家禽中持续存在,给家禽养殖业带来巨大经济损失;H9N2亚型AIV偶尔会感染人和哺乳动物,并且H9N2亚型AIV可为HPAIV如H5N1、H7N9和H10N8病毒提供内部基因,对哺乳动物的感染性和对人类的潜在威胁备受关注。

  本研究于2016-2019年间在山东及周边地区不同养殖场分离鉴定了21株 H9N2亚型AIV,大多数分离株对哺乳动物高度适应,可以在小鼠的肺部复制良好并引起肺脏病理损伤;病毒在MDCK细胞中的增殖能力和对肺组织损伤程度与其在小鼠肺脏内滴度相对应。基因遗传进化分析表明:21株H9N2亚型AIV分离株属于同一个基因型G57型,并含有很多已被证明为禽类-哺乳动物跨物种感染标志的氨基酸突变或缺失。此外,研究新发现7个病毒蛋白中的9个氨基酸残基与H9N2亚型AIV分离株在哺乳动物中的复制表型相关。本研究为家禽养殖业科学防控H9N2亚型禽流感以及进一步研究H9N2亚型AIV跨种传播提供研究背景。

  山东师范大学硕士研究生陈召坤和山东省农业科学院畜牧兽医研究所助理研究员黄庆华为论文第一作者,许传田研究员和崔宁助理研究员为共同通讯作者。该研究得到了国家重点研发计划(2016YFD0500201)、山东省农业科学院高层次人才和创新团队引进计划(CXGC2018E10)、现代农业产业技术体系建设专项资金(CARS-41-Z10)等基金的资助。

  Abstract: H9N2 subtype avian influenza virus (AIV) is widely prevalent in poultry, and the virus is becoming adaptive to mammals, which poses pandemic importance. Here, BALB/c mice were employed as a model to evaluate the adaption in mammals of 21 field H9N2 viruses isolated from avian species between 2016 to 2019 in China. The replication capacity of the viruses was evaluated in the lungs of mice. The pathogenicity of the viruses were compared by weight loss and lung lesions from infected mice. The whole genomic sequences of the viruses were further characterized to define the associated phenotypes of the H9N2 viruses in vitro and in vivo. The results showed that most viruses could replicate well and cause lesions in the mouse lungs. The propagation capacity in MDCK cells and damage to respiratory tissues of the infected mice corresponded to relative viral titers in the mouse lungs. Further genome analysis showed that all of the H9N2 viruses belonged to the same genotype, G57, and contained a couple of amino acid substitutions or deletions that have been demonstrated as avian-human markers. Additionally, nine amino acids residues in seven viral proteins were found to be correlated with the replication phenotypes of the H9N2 viruses in mammals. The study demonstrated that a well-defined H9N2 AIV genotype with high adaption in mammals was prevalent in China in recent years. Further investigations on the role of the identified residues and continuous surveillance of newly identified mutations associated with host adaption should be strengthened to prevent any devastating human influenza pandemics.

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