The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host
The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host
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DOI：
10.1073/pnas.0507415102
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发表时间：
2005-12-20
影响因子：
11.1
通讯作者：
Stech, J
中科院分区：
文献类型：
--
作者：
Gabriel, G;Dauber, B;Stech, J
哺乳动物流感病毒是禽流感病毒株的后代，它们跨越了物种障碍并经历了进一步的适应。自1997年以来，H5N1高致病性禽流感病毒在东南亚一直给人类带来严重甚至致命的疾病。尽管迄今为止尚未确定该亚型的谱系，但此类重复事件可能会引发新的大流行。作为物种传播模型，我们使用对小鼠低致病性的高致病性禽流感病毒 SC35 (H7N7) 及其致命的小鼠后代 SC35M。 SC35M 聚合酶的特定突变大大增加了其在哺乳动物细胞中的活性，与小鼠中的高毒力相关。其中一些突变在鸡和哺乳动物分离株中普遍存在，特别是在来自东南亚的高致病性 H5N1 病毒中。病毒聚合酶复合物的这些增强活性的突变证明了自然界的趋同进化，因此可能是适应新宿主的先决条件，为新的大流行病毒铺平了道路。
Mammalian influenza viruses are descendants of avian strains that crossed the species barrier and underwent further adaptation. Since 1997 in southeast Asia, H5N1 highly pathogenic avian influenza viruses have been causing severe, even fatal disease in humans. Although no lineages of this subtype have been established until now, such repeated events may initiate a new pandemic. As a model of species transmission, we used the highly pathogenic avian influenza virus SC35 (H7N7), which is low-pathogenic for mice, and its lethal mouse-adapted descendant SC35M. Specific mutations in SC35M polymerase considerably increase its activity in mammalian cells, correlating with high virulence in mice. Some of these mutations are prevalent in chicken and mammalian isolates, especially in the highly pathogenic H5N1 viruses from southeast Asia. These activity-enhancing mutations of the viral polymerase complex demonstrate convergent evolution in nature and, therefore, may be a prerequisite for adaptation to a new host paving the way for new pandemic viruses.