Chicken-derived MERTK protein inhibits Newcastle disease virus replication by increasing STAT1 phosphorylation in DF-1 cells

文献类型： 外文期刊

第一作者： Tan, Lei

作者： Tan, Lei;Huang, Meizhen;Qiu, Xusheng;Zhi, Xuechun;Liang, Lujing;Sun, Yingjie;Liao, Ying;Song, Cuiping;Ding, Chan;Tan, Lei;Ren, Tao;Ding, Chan

作者机构：

关键词： Receptor tyrosine kinase; MERTK; Newcastle disease virus (NDV); Signal transducer and activator of transcription; 1 (STAT1); Casitas B -lineage proto-oncogene (CBL)

期刊名称：VIRUS RESEARCH （ 影响因子：5.0； 五年影响因子：4.0 ）

ISSN： 0168-1702

年卷期： 2023 年 326 卷

页码：

收录情况： SCI

摘要： The receptor tyrosine kinases TYRO3, AXL, and MERTK (TAM) are transmembrane proteins associated with the regulation of the innate immune response. In this study, the role of the chicken-derived MERTK protein (chMertk) in the regulation of the type I interferon (IFN) signaling pathway and its antiviral effect were investigated in vitro. Newcastle disease (ND) caused by the Newcastle disease virus (NDV) is able to widely spread in chickens and give rise to massive losses in the poultry industry around the world. We found that the overexpression of the exogenous chMertk upregulated the STAT1 phosphorylation and the expression of IFNstimulated gene IFITM3 and significantly reduced the NDV titer (p < 0.05). A mutation assay showed that three tyrosine residues (Y739, Y743, and Y744) in chMertk promoted STAT1 phosphorylation and inhibited NDV replication. However, the chicken-derived E3 ubiquitin ligase CBL significantly negatively regulated chMertk expression, thus attenuating STAT1 phosphorylation. chMertk function was restored by the ubiquitin-proteasome inhibitor MG132, demonstrating that chMertk was controlled by Casitas B-lineage proto-oncogene (CBL) ubiquitination and degradation. Together, these results suggested that chMertk participated in regulating the immune responses to NDV infection, and that CBL significantly downregulated the expression of chMertk through its ubiquitination and degradation, to maintain cellular homeostasis. Overall, our study provided new insights into the role of chMertk in regulating the innate immune response and its anti-NDV activity.

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