Full factorial analysis of mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation.
Full factorial analysis of mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation.
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DOI：
10.1371/journal.pone.0005658
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发表时间：
2009-05-21
期刊：
影响因子：
3.7
通讯作者：
Poon LL
中科院分区：
文献类型：
--
作者：
Li OT;Chan MC;Leung CS;Chan RW;Guan Y;Nicholls JM;Poon LL
在所有内部基因片段（PB 2. PB 1、PA、NP、M和NS），禽PB 1片段是唯一一个重配成人H2 N2和H3 N2大流行毒株的片段。这表明，哺乳动物和禽流感病毒之间的聚合酶亚单位基因的重排可能在种间传播中发挥作用。为了验证这一假设，我们测试了来自H5 N1病毒和哺乳动物H1N1病毒的PB 2、PB 1、PA和NP之间的相容性。所有16个可能的组合的禽-哺乳动物嵌合病毒核糖核蛋白（vRNP）的特点。我们发现，重组vRNP与哺乳动物PB 2和禽PB 1在人类细胞中的聚合酶活性最强，在所有研究的温度。此外，具有这种特定PB 2-PB 1组合的病毒可以在细胞培养物中有效生长，特别是在高孵育温度下。这些病毒是原代人巨噬细胞和肺细胞中促炎细胞因子和趋化因子的强效诱导剂。还发现具有这种特定PB 2-PB 1组合的病毒在新的选择压力下更能够产生适应性突变。这些结果表明，病毒聚合酶活性可能与人类健康关注的流感病毒的发生有关。
Amongst all the internal gene segments (PB2. PB1, PA, NP, M and NS), the avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis, we tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature. These viruses were potent inducers of proinflammatory cytokines and chemokines in primary human macrophages and pneumocytes. Viruses with this specific PB2-PB1 combination were also found to be more capable to generate adaptive mutations under a new selection pressure. These results suggested that the viral polymerase activity might be relevant for the genesis of influenza viruses of human health concern.
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DOI：
10.1073/pnas.031575198
发表时间：
2001-02-27
影响因子：
11.1
作者：
Basler, CF;Reid, AH;Taubenberger, JK
通讯作者：
Taubenberger, JK
影响因子：
5.4
作者：
Fodor, E;Smith, M
通讯作者：
Smith, M
影响因子：
64.8
作者：
ALMOND, JW
通讯作者：
ALMOND, JW
影响因子：
3.7
作者：
Digard P;Blok VC;Inglis SC
通讯作者：
Inglis SC
影响因子：
5.4
作者：
Chen, HL;Li, YB;Kawaoka, Y
通讯作者：
Kawaoka, Y