Comparative Proteomic Analysis of Wild-Type and SAP Domain Mutant Foot-and-Mouth Disease Virus-Infected Porcine Cells Identifies the Ubiquitin-Activating Enzyme UBE1 Required for Virus Replication

文献类型: 外文期刊

第一作者: Zhu, Zixiang

作者: Zhu, Zixiang;Yang, Fan;Zhang, Keshan;Cao, Weijun;Jin, Ye;Wang, Guoqing;Mao, Ruoqing;Li, Dan;Guo, Jianhong;Liu, Xiangtao;Zheng, Haixue

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关键词: foot-and-mouth disease virus;SAP domain;iTRAQ;quantitative proteomics;pathway analysis

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

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收录情况: SCI

摘要: Leader protein (L-Pro) of foot-and-mouth disease virus (FMDV) manipulates the activities of several host proteins to promote viral replication and pathogenicity. L-Pro has a conserved protein domain SAP that is suggested to subvert interferon (IFN) production to block antiviral responses. However, apart from blocking IFN production, the roles of the SAP domain during FMDV infection in host cells remain unknown. Therefore, we identified host proteins associated with the SAP domain of L-Pro by a high-throughput quantitative proteomic approach [isobaric tags for relative and absolute quantitation (iTRAQ) in conjunction with liquid chromatography/electrospray ionization tandem mass spectrometry]. Comparison of the differentially regulated proteins in rA/FMDVA Delta mSAP- versus rA/FMDV-infected SK6 cells revealed 45 down-regulated and 32 up-regulated proteins that were mostly associated with metabolic, ribosome, spliceosome, and ubiquitin-proteasome pathways. The results also imply that the SAP domain has a function similar to SAP-A/B besides its potential protein inhibitor of activated signal transducer and activator of transcription (PIAS) function. One of the identified proteins UBE1 was further analyzed and displayed a novel role for the SAP domain of L-Pro. Overexpression of UBE1 enhanced the replication of FMDV, and knockdown of UBE1 decreased FMDV replication. This shows that FMDV manipulates UBE1 for increased viral replication, and the SAP domain was involved in this process.

分类号: Q7`Q51

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