State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Virus Res. 2021 Jan 2;291:198186. doi: 10.1016/j.virusres.2020.198186. Epub 2020 Oct 16.
Characterization of host adaptation markers among human isolates is important for recognizing the potential for cross-species transmission in avian influenza A viruses. Here, we studied two new potential adaptive mutations, V292I and D740A, in the PB2 protein that were identified by a multi-factor regression model. The study shows that the prevalence of the PB2-V292I mutation is increased in H7N9 influenza viruses isolated from both humans and birds over the past 6 years. The phylogenetic tree showed that influenza A/H7N9 has a lineage based on the strains containing PB2-292I. Polymerase complexes containing PB2-292I/627K derived from H7N9 exhibit increased polymerase activity. PB2-292I coupled with 627K also enhances viral transcription and replication in cells, whereas PB2-292I alone did not show the same effect in the H7N9 virus. However, PB2-740A only had a limited prevalence in 2013, and the change from D to A in PB2-740A may have a negative effect on the replication of the H7N9 virus in cells.
鉴定人类分离株中的宿主适应标记对于识别禽流感病毒在物种间传播的潜力非常重要。在这里，我们通过多因素回归模型研究了 PB2 蛋白中两个新的潜在适应性突变 V292I 和 D740A。研究表明，过去 6 年中，从人和鸟类中分离出的 H7N9 流感病毒中 PB2-V292I 突变的流行率增加。系统发育树显示，基于包含 PB2-292I 的株系，流感 A/H7N9 具有一个谱系。源自 H7N9 的包含 PB2-292I/627K 的聚合酶复合物显示出增强的聚合酶活性。PB2-292I 与 627K 结合也增强了细胞中的病毒转录和复制，而单独的 PB2-292I 在 H7N9 病毒中没有显示出相同的效果。然而，PB2-740A 仅在 2013 年有有限的流行率，并且 PB2-740A 中的 D 到 A 的变化可能对 H7N9 病毒在细胞中的复制产生负面影响。
