Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses

Genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza A viruses
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DOI:
10.1099/0022-1317-81-5-1283
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发表时间:
2000-05-01
影响因子:
3.8
通讯作者:
van der Werf, S
van der Werf, S
中科院分区:
医学3区
文献类型:
--
作者:
Naffakh, N;Massin, P;van der Werf, S

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为了确定来自人类和禽流感A型病毒的聚合酶蛋白在哺乳动物细胞中相互作用的效率,使用了一种允许活性核糖核蛋白在体内重组的遗传系统。用核心蛋白(PB1、PB2、PB2、PB1)的异源混合物检测COS-1细胞中病毒样报告RNA的复制能力。PA和NP)从两个菌株的人类病毒(/波多黎各/ 8/34 /维多利亚/ 3/75),两种禽流感病毒(/野鸭/纽约/ 6750/78 /废票/罗斯托克/ 34),和一个应变的鸟类起源(/香港/ 156/97)隔绝第一例H5N1流感于1997年在香港,按照发表对重组病毒,PB2氨基酸627年被确认为heterospecific复合物的复制效率的主要决定因素在COS-1细胞中,此外,研究结果还表明,当PB2和NP均来源于同一禽类或人类病毒时,或者当PB1来源于禽类病毒时,无论其他蛋白的来源如何,病毒样报告RNA的复制效率更高。此外,A/ hong kong /156/97病毒的PB1和PB2蛋白相对于禽类或人类流感病毒的相应蛋白表现出中间特性。这表明PB1和PB2蛋白的某些分子特征可能至少部分解释了A/Hong Kong/156/97病毒在人体内复制的能力。
In order to determine how efficiently the polymerase proteins derived from human and avian influenza A viruses can interact with each other in the context of a mammalian cell, a genetic system that allows the in vivo reconstitution of active ribonucleoproteins was used, The ability to achieve replication of a viral-like reporter RNA in COS-1 cells was examined with heterospecific mixtures of the core proteins (PB1, PB2, PA and NP) from two strains of human viruses (A/Puerto Rico/8/34 and A/Victoria/3/75), two strains of avian viruses (A/Mallard/NY/6750/78 and A/FPV/Rostock/34), and a strain of avian origin (A/Hong Kong/156/97) that was isolated from the first human case of H5N1 influenza in Hong Kong in 1997, In accordance with published observations on reassortant viruses, PB2 amino acid 627 was identified as a major determinant of the replication efficiency of heterospecific complexes in COS-1 cells, Moreover, the results showed that replication of the viral-like reporter RNA was more efficient when PB2 and NP were both derived from the same avian or human virus or when PB1 was derived from an avian virus, whatever the origin of the other proteins, Furthermore, the PB1 and PB2 proteins from the A/Hong-Kong/156/97 virus exhibited intermediate properties with respect to the corresponding proteins from avian or human influenza viruses, suggesting that some molecular characteristics of PB1 and PB2 proteins might at least partially account for the ability of the A/Hong Kong/156/97 virus to replicate in humans.