Characterization of the 1918 influenza virus polymerase genes
Characterization of the 1918 influenza virus polymerase genes
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DOI：
10.1038/nature04230
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发表时间：
2005-10-06
期刊：
影响因子：
64.8
通讯作者：
Fanning, TG
中科院分区：
文献类型：
--
作者：
Taubenberger, JK;Reid, AH;Fanning, TG
已知甲型流感病毒异源三聚体聚合酶复合物（PA、PB 1、PB 2）参与病毒复制的许多方面，并与宿主因子相互作用（1），从而在宿主特异性中发挥作用（2、3）。来自1918年人类流感病毒的聚合酶蛋白序列与禽类共有序列仅在少量氨基酸上不同，这与它们在大流行前不久来自禽类来源的假设一致。然而，当与禽类序列相比时，1918聚合酶基因的核苷酸序列具有比预期更多的同义差异，表明与已知禽类菌株的进化距离。在此，我们对1918年流感病毒的全基因组进行了测序和系统发育分析（4-8），并提出1918年的病毒不是一种可抵抗的病毒（如1957年和1968年的流感大流行病毒（9，10）），而更可能是一种适应人类的完全类似禽类的病毒。这些数据支持先前的系统发育研究，表明1918年病毒来源于禽类（11）。聚合酶蛋白中总共10个氨基酸的变化始终将1918年和随后的人流感病毒序列与禽流感病毒序列区分开来。值得注意的是，在最近流行的高致病性H5 N1病毒中也发现了一些相同的变化，这些病毒已导致人类患病和死亡，并被担心是新流感大流行的前兆。这里确定的序列变化可能对流感病毒适应人类很重要。
The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors(1), thereby having a role in host specificity(2,3). The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian sequences, the nucleotide sequences of the 1918 polymerase genes have more synonymous differences than expected, suggesting evolutionary distance from known avian strains. Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus(4-8), and propose that the 1918 virus was not a reassortant virus ( like those of the 1957 and 1968 pandemics(9,10)), but more likely an entirely avian-like virus that adapted to humans. These data support prior phylogenetic studies suggesting that the 1918 virus was derived from an avian source(11). A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.