Quantitative Proteomics Reveals a Novel Role of the E3 Ubiquitin-Protein Ligase FANCL in the Activation of the Innate Immune Response through Regulation of TBK1 Phosphorylation during Peste des Petits Ruminants Virus Infection

文献类型： 外文期刊

第一作者： Chen, Shuying

作者： Chen, Shuying;Wen, Bo;Wang, Jingyu;Chen, Shuying;Yang, Fan;Cao, Weijun;Liu, Huisheng;Sun, Yuefeng;Zheng, Haixue;Zhu, Zixiang

作者机构：

关键词： peste des petits ruminants virus; quantitative proteomics; FANCL; innate immune response; TBK1

期刊名称：JOURNAL OF PROTEOME RESEARCH （ 影响因子：4.466； 五年影响因子：4.352 ）

ISSN： 1535-3893

年卷期： 2021 年 20 卷 8 期

页码：

收录情况： SCI

摘要： Peste des petits ruminants virus (PPRV) infection causes considerable innate immunosuppression in its host, which promotes viral replication. However, how the host rescues the innate immune response to counteract this immunosuppression during viral replication remains largely unknown. To explore the mechanisms of how a host counteracts PPRV-mediated innate immunosuppression, a high-throughput quantitation proteomic approach (isobaric tags for relative and absolute quantitation in conjunction with LC-MS/MS) was used to investigate the proteome landscape of goat fetal fibroblasts (GFFs) in response to PPRV infection. Eventually, 497 upregulated proteins and 358 downregulated proteins were identified. Many of the differentially expressed proteins were enriched in immune-related pathways. Blocking the activation of the innate immune response with a specific inhibitor BX795 in GFFs remarkably promoted PPRV replication, suggesting the significant antiviral role of the enriched immune-related pathways. The GO enrichment analysis showed that the host protein FANCL revealed a similar expression pattern to these innate immune-related proteins. In addition, the analysis of protein-protein interaction networks reveals a potential relationship between FANCL and the innate immune pathway. We determined that FANCL inhibited PPRV infection by enhancing type I interferon (IFN) and IFN-stimulated gene expression. Further investigation determined that FANCL induced type I IFN production by promoting TBK1 phosphorylation, thus impairing PPRV-mediated immunosuppression.

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