326K at E Protein Is Critical for Mammalian Adaption of TMUV

文献类型： 外文期刊

第一作者： Liu, Xingpo

作者： Liu, Xingpo;Yan, Dawei;Zhang, Yuee;Xu, Bangfeng;Li, Luzhao;Shi, Xiaona;Ma, Tianxin;Li, Xuesong;Teng, Qiaoyang;Yuan, Chunxiu;Liu, Qinfang;Li, Zejun;Peng, Shan

作者机构：

关键词： Tembusu virus; envelope protein; mutation; inflammatory; RIG-I-IRF7

期刊名称：VIRUSES-BASEL （ 影响因子：4.7； 五年影响因子：4.8 ）

ISSN：

年卷期： 2023 年 15 卷 12 期

页码：

收录情况： SCI

摘要： Outbreaks of Tembusu virus (TMUV) infection have caused huge economic losses to the poultry industry in China since 2010. However, the potential threat of TMUV to mammals has not been well studied. In this study, a TMUV HB strain isolated from diseased ducks showed high virulence in BALB/c mice inoculated intranasally compared with the reference duck TMUV strain. Further studies revealed that the olfactory epithelium is one pathway for the TMUV HB strain to invade the central nervous system of mice. Genetic analysis revealed that the TMUV HB virus contains two unique residues in E and NS3 proteins (326K and 519T) compared with duck TMUV reference strains. K326E substitution weakens the neuroinvasiveness and neurovirulence of TMUV HB in mice. Remarkably, the TMUV HB strain induced significantly higher levels of IL-1 beta, IL-6, IL-8, and interferon (IFN)-alpha/beta than mutant virus with K326E substitution in the brain tissue of the infected mice, which suggested that TMUV HB caused more severe inflammation in the mouse brains. Moreover, application of IFN-beta to infected mouse brain exacerbated the disease, indicating that overstimulated IFN response in the brain is harmful to mice upon TMUV infection. Further studies showed that TMUV HB upregulated RIG-I and IRF7 more significantly than mutant virus containing the K326E mutation in mouse brain, which suggested that HB stimulated the IFN response through the RIG-I-IRF7 pathway. Our findings provide insights into the pathogenesis and potential risk of TMUV to mammals.

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