NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response

NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response
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DOI:
10.1128/jvi.01856-06
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发表时间:
2007-03-01
影响因子:
5.4
通讯作者:
Barclay, W. S.
Barclay, W. S.
中科院分区:
医学2区
文献类型:
--
作者:
Hayman, A.;Comely, S.;Barclay, W. S.

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许多病毒,包括人类甲型流感病毒,已经开发出对抗宿主I型干扰素(干扰素)反应的策略。我们已经探索了禽流感病毒在哺乳动物细胞中对抗I型干扰素反应的能力是否较弱,因为这可能是宿主范围限制的一个决定因素。组装了1927年至1997年期间分离的禽流感病毒的专家小组。选定的病毒在干扰素-β启动子控制下激活报告基因表达的能力和在哺乳动物细胞中诱导的干扰素水平显示出差异。令人惊讶的是,单独表达或在人类流感病毒遗传背景中表达的禽类NS1蛋白控制着干扰素-β的诱导,其方式类似于人类菌株的NS1蛋白。禽流感病毒在人A549细胞中的复制与干扰素-β的诱导作用没有直接关系。然而,缺乏I型干扰素系统的人类细胞显示出对所研究的禽流感病毒的复制增强,这意味着人类I型干扰素反应限制了禽流感病毒,并可能有助于限制宿主的范围。
Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-beta promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-beta induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-beta induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.