Li Olive T W, Chan Michael C W, Leung Cynthia S W, Chan Renee W Y, Guan Yi, Nicholls John M, Poon Leo L M
State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China.
PLoS One. 2009 May 21;4(5):e5658. doi: 10.1371/journal.pone.0005658.
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.
在所有内部基因片段（PB2、PB1、PA、NP、M和NS）中，禽源PB1片段是唯一重配到人类H2N2和H3N2大流行毒株中的片段。这表明哺乳动物和禽流感病毒之间聚合酶亚基基因的重配可能在种间传播中起作用。为了验证这一假设，我们测试了源自H5N1病毒和哺乳动物H1N1病毒的PB2、PB1、PA和NP之间的兼容性。对禽-哺乳动物嵌合病毒核糖核蛋白（vRNP）的所有16种可能组合进行了表征。我们发现，在所有研究温度下，具有哺乳动物PB2和禽源PB1的重组vRNP在人细胞中具有最强的聚合酶活性。此外，具有这种特定PB2-PB1组合的病毒能够在细胞培养物中高效生长，尤其是在较高的孵育温度下。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有效诱导剂。还发现具有这种特定PB2-PB1组合的病毒在新的选择压力下更有能力产生适应性突变。这些结果表明，病毒聚合酶活性可能与对人类健康构成威胁的流感病毒的产生有关。
