Double mutations in the H9N2 avian influenza virus PB2 gene act cooperatively to increase viral host adaptation and replication for human infections
Double mutations in the H9N2 avian influenza virus PB2 gene act cooperatively to increase viral host adaptation and replication for human infections
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DOI：
10.1099/jgv.0.001612
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发表时间：
2021-01-01
影响因子：
3.8
通讯作者：
Watanabe, Yohei
中科院分区：
文献类型：
--
作者：
Elgendy, Emad Mohamed;Arai, Yasuha;Watanabe, Yohei
东亚地区的H9N2型禽流感病毒具有基因多样性，并已在家禽中建立了多种基因类型(A-W)。S基因型毒株是目前最流行的毒株，已引起多人感染，并对公众健康构成威胁。在本研究中，通过数据库筛选鉴定了S基因型毒株中PB2聚合酶的人类适应性突变。已鉴定出几个PB2双突变，它们协同作用，在人类细胞中产生比在禽类细胞中更高的S病毒聚合酶活性和复制，并在小鼠中增加病毒的生长和毒力。这些突变在时间上和系统发育上都聚集在S基因内的一个新的组中。大多数相关的人类病毒分离株携带PB2-A588V突变和另一种PB2突变(即K526R、E627V或E627K)，表明这些双重突变具有宿主适应优势。在基因相关的人H7N9和H10N8病毒中，也发现了人H9N2病毒分离株中PB2双突变的流行。这些结果表明，现场病毒中的PB2双突变协同作用，提高了目前流行的H9N2型S毒株的人类适应能力。这可能是导致最近H9N2感染激增的原因之一，也可能适用于人类对其他几种禽流感病毒的适应。我们的研究为人类对自然界中遗传相关的H9N2、H7N9和H10N8病毒的适应途径提供了更好的理解。
Avian H9N2 influenza viruses in East Asia are genetically diversified and multiple genotypes (A-W) have been established in poultry. Genotype S strains are currently the most prevalent strains, have caused many human infections and pose a public health threat. In this study, human adaptation mutations in the PB2 polymerase in genotype S strains were identified by database screening. Several PB2 double mutations were identified that acted cooperatively to produce higher genotype S virus polymerase activity and replication in human cells than in avian cells and to increase viral growth and virulence in mice. These mutations were chronologically and phylogenetically clustered in a new group within genotype S viruses. Most of the relevant human virus isolates carry the PB2-A588V mutation together with another PB2 mutation (i.e. K526R, E627V or E627K), indicating a host adaptation advantage for these double mutations. The prevalence of PB2 double mutations in human H9N2 virus isolates has also been found in genetically related human H7N9 and H10N8 viruses. These results suggested that PB2 double mutations in viruses in the field acted cooperatively to increase human adaptation of the currently prevalent H9N2 genotype S strains. This may have contributed to the recent surge of H9N2 infections and may be applicable to the human adaptation of several other avian influenza viruses. Our study provides a better understanding of the human adaptation pathways of genetically related H9N2, H7N9 and H10N8 viruses in nature.