Glutamic Acid at Position 343 in PB2 Contributes to the Virulence of H1N1 Swine Influenza Virus in Mice

文献类型： 外文期刊

第一作者： Wang, Yanwen

作者： Wang, Yanwen;Zhong, Qiu;Meng, Fei;Cheng, Zhang;Zhang, Yijie;Song, Zuchen;Zhang, Yali;Feng, Zijian;Zhai, Yujia;Chen, Yan;Qiao, Chuanling;Yang, Huanliang

作者机构：

关键词： influenza virus; PB2; molecular basis; pathogenicity

期刊名称：VIRUSES-BASEL （ 影响因子：3.5； 五年影响因子：3.7 ）

ISSN：

年卷期： 2025 年 17 卷 7 期

页码：

收录情况： SCI

摘要： The H1N1 swine influenza viruses CQ91 and CQ445, isolated from pigs in China, exhibited distinct virulence in mice despite sharing similar genomic constellations. CQ91 demonstrated higher pathogenicity (MLD50: 5.4 log(10) EID50) and replication efficiency in mice compared to CQ445 (MLD50: 6.6 log(10) EID50). Through reverse genetics, we found that the attenuation of CQ445 was due to a single substitution of glutamic acid (E) with lysine (K) at position 343 in the PB2 protein. Introducing the CQ445-PB2 (343K) into CQ91 significantly reduced viral replication and pathogenicity in mice, while replacing CQ445-PB2 with CQ91-PB2 (343E) restored virulence. In vitro studies showed that the K343E mutation impaired viral replication in MDCK and A549 cells and reduced polymerase activity in minigenome assays. Mechanistically, the amino acid at position 343 in the PB2 affects the transcription stage of the viral replication process. Structural modeling indicated that the charge reversal caused by E343K altered local electrostatic interactions without major conformational changes. Phylogenetic analysis revealed that PB2-343E is highly conserved (>99.9%) in human and swine H1/H3 influenza viruses, suggesting that PB2-343E confers an adaptive advantage. This study identifies PB2-343E as a critical determinant of influenza virus pathogenicity in mammals, highlighting its role in host adaptation.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序