Human influenza A viral genes responsible for the restriction of its replication in duck intestine

Human influenza A viral genes responsible for the restriction of its replication in duck intestine
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DOI:
10.1006/viro.2002.1358
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发表时间:
2002-04-10
期刊:
影响因子:
3.7
通讯作者:
Kawaoka, Y
Kawaoka, Y
中科院分区:
医学3区
文献类型:
--
作者:
Hatta, M;Halfmann, P;Kawaoka, Y

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虽然甲型流感病毒偶尔会从一种动物传播到另一种动物,但其宿主范围往往受到限制,目前流行的人类甲型流感病毒被认为来自禽类病毒,但这些毒株都没有在禽类病毒复制的主要部位鸭肠内复制。虽然已知血凝素(HA)和神经氨酸酶(NA)基因限制人病毒在鸭体内的复制,但其他病毒基因的作用尚不清楚,以确定人甲型流感病毒在鸭肠内复制的宿主范围限制的遗传基础。我们首先建立了一个反向遗传学系统,用于从克隆的cDNA中产生A/孟菲斯/8/88(H3N 2)(Mem/88)和A/Mallard/New York/6750/78(H_2N_2)(Mal/NY)病毒。然后利用这个系统,我们试图产生具有各种候选基因组合的重配病毒。我们从Mem/88获得了含有PB2、NP、M或INS的单基因重组体,其余的来自MAL/NY。尽管没有从Mem/88获得其他单基因重组体,但我们确实产生了由HA和NA、全部三个聚合酶基因(PB2、PB1和PA)或所有的聚合酶基因和Mem/88的NP基因组成的重配病毒,其余的来自Mem/88的Mal/NY,仅具有Mem/88的M或Ins基因,其余的来自Mal/NY,其余的由Mem/88的M或Ins基因组成,其余的来自Mal/NY。这些结果表明禽流感病毒和人类甲型流感病毒的基因不相容,表明除M和INS基因外,其他所有基因都限制了人甲型流感病毒在鸭肠内的复制。(C)2002年埃尔塞维尔科学公司(美国)。
Although influenza A viruses are occasionally transmitted from one animal species to another, their host range tends to be restricted, Currently circulating human influenza A viruses are thought to have originated from avian viruses, yet none of these strains replicate in duck intestine, a major site of avian virus replication, Although the hemagglutinin (HA) and neuraminidase (NA) genes are known to restrict human virus replication in ducks, the contribution of the other viral genes remains unknown To determine the genetic basis for host range restriction of the replication of human influenza A virus in duck intestine, we first established a reverse genetics system for generating A/Memphis/8/88 (H3N2) (Mem/88) and A/mallard/New York/6750/78 (H2N2) (Mal/NY) viruses from cloned cDNAs. Using this system, we then attempted to generate reassortant viruses with various combinations of candidate genes. We were able to generate single-gene reassortants, which possessed PB2, NP, M, or INS from Mem/88, with the remainder from Mal/NY Despite unsuccessful production of other single-gene reassortants from Mem/88 we did generate reassortant viruses comprised of both the HA and the NA, all three polymerase genes (PB2, PB1, and PA), or all polymerase genes and the NP gene from Mem/88, with the rest derived from Mal/NY Among these reassortants, only those possessing the M or INS gene from Mem/88 and the remainder from Mal/NY replicated in duck intestine. These results indicate incompatibility between the genes of avian and human influenza A viruses and indicate that all genes other than the M and INS restrict replication of human influenza A virus in duck intestine. (C) 2002 Elsevier Science (USA).