Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus.
Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus.
复制标题
禽 H5N1 流感病毒聚合酶复合物中哺乳动物适应突变的鉴定。
DOI：
10.1038/ncomms8491
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发表时间：
2015-06-17
影响因子：
16.6
通讯作者：
Kawaoka Y
中科院分区：
文献类型：
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作者：
Taft AS;Ozawa M;Fitch A;Depasse JV;Halfmann PJ;Hill-Batorski L;Hatta M;Friedrich TC;Lopes TJ;Maher EA;Ghedin E;Macken CA;Neumann G;Kawaoka Y
H5 N1亚型禽流感病毒由于与由这些病毒引起的疾病相关的高死亡率（>60%）以及在一般人群中缺乏针对这些病毒的保护性抗体而构成严重的全球健康威胁。使禽H5 N1流感病毒能够在人类中复制的因素尚未完全了解。在这里，我们使用高通量筛选方法，以确定新的突变的聚合酶基因的禽H5 N1病毒，赋予有效的聚合酶活性的哺乳动物细胞。与野生型病毒相比，几种已鉴定的突变（以前在天然分离株中发现）增加了哺乳动物细胞中的病毒复制和感染小鼠的毒力。鉴定禽H5 N1流感病毒聚合酶复合体中赋予哺乳动物增加的复制和毒力的氨基酸突变对于鉴定感染人类的可能性增加的流行H5 N1病毒是重要的。本文的在线版本（doi：10.1038/ncomms 8491）包含补充材料，授权用户可以使用。了解使某些禽流感病毒感染人类的因素对于识别更有可能感染我们的流行病毒非常重要。在此，塔夫脱等鉴定了禽H5 N1病毒聚合酶中的新突变，其有助于病毒在人细胞和小鼠中复制.本文的在线版本（doi：10.1038/ncomms 8491）包含补充材料，授权用户可获得.
Avian influenza viruses of the H5N1 subtype pose a serious global health threat due to the high mortality (>60%) associated with the disease caused by these viruses and the lack of protective antibodies to these viruses in the general population. The factors that enable avian H5N1 influenza viruses to replicate in humans are not completely understood. Here we use a high-throughput screening approach to identify novel mutations in the polymerase genes of an avian H5N1 virus that confer efficient polymerase activity in mammalian cells. Several of the identified mutations (which have previously been found in natural isolates) increase viral replication in mammalian cells and virulence in infected mice compared with the wild-type virus. The identification of amino-acid mutations in avian H5N1 influenza virus polymerase complexes that confer increased replication and virulence in mammals is important for the identification of circulating H5N1 viruses with an increased potential to infect humans. The online version of this article (doi:10.1038/ncomms8491) contains supplementary material, which is available to authorized users. Understanding the factors that enable some bird flu viruses to infect humans is important for the identification of circulating viruses with higher potential to infect us. Here, Taft et al.identify novel mutations in the polymerase of an avian H5N1 virus that help the virus to replicate in human cells and in mice The online version of this article (doi:10.1038/ncomms8491) contains supplementary material, which is available to authorized users.