TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein

Nuclear localization of cytoplasmic RNA virus proteins mediated by intrinsic nuclear localization signal (NLS) plays essential roles in successful virus replication. We previously reported that NLS mutation in the matrix (M) protein obviously attenuates the replication and pathogenicity of Newcastle...

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Autores principales:	Zhiqiang Duan, Chao Yuan, Yifan Han, Lei Zhou, Jiafu Zhao, Yong Ruan, Jiaqi Chen, Mengmeng Ni, Xinqin Ji
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	newcastle disease virus matrix protein nuclear localization signal nucleocytoplasmic trafficking tmt quantitative proteomics Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/39168f0e1b27410e8d645f0c2dea02d4
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spelling	oai:doaj.org-article:39168f0e1b27410e8d645f0c2dea02d42021-11-17T14:21:58ZTMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein2150-55942150-560810.1080/21505594.2020.1770482https://doaj.org/article/39168f0e1b27410e8d645f0c2dea02d42020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1770482https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Nuclear localization of cytoplasmic RNA virus proteins mediated by intrinsic nuclear localization signal (NLS) plays essential roles in successful virus replication. We previously reported that NLS mutation in the matrix (M) protein obviously attenuates the replication and pathogenicity of Newcastle disease virus (NDV), but the attenuated replication mechanism remains unclear. In this study, we showed that M/NLS mutation not only disrupted M’s nucleocytoplasmic trafficking characteristic but also impaired viral RNA synthesis and transcription. Using TMT-based quantitative proteomics analysis of BSR-T7/5 cells infected with the parental NDV rSS1GFP and the mutant NDV rSS1GFP-M/NLSm harboring M/NLS mutation, we found that rSS1GFP infection stimulated much greater quantities and more expression changes of differentially expressed proteins involved in host cell transcription, ribosomal structure, posttranslational modification, and intracellular trafficking than rSS1GFP-M/NLSm infection. Further in-depth analysis revealed that the dominant nuclear accumulation of M protein inhibited host cell transcription, RNA processing and modification, protein synthesis, posttranscriptional modification and transport; and this kind of inhibition could be weakened when most of M protein was confined outside the nucleus. More importantly, we found that the function of M protein in the cytoplasm effected the inhibition of TIFA expression in a dose-dependent manner, and promoted NDV replication by down-regulating TIFA/TRAF6/NF-κB-mediated production of cytokines. It was the first report about the involvement of M protein in NDV immune evasion. Taken together, our findings demonstrate that NDV replication is closely related to the nucleocytoplasmic trafficking of M protein, which accelerates our understanding of the molecular functions of NDV M protein.Zhiqiang DuanChao YuanYifan HanLei ZhouJiafu ZhaoYong RuanJiaqi ChenMengmeng NiXinqin JiTaylor & Francis Grouparticlenewcastle disease virusmatrix proteinnuclear localization signalnucleocytoplasmic traffickingtmtquantitative proteomicsInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 607-635 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	newcastle disease virus matrix protein nuclear localization signal nucleocytoplasmic trafficking tmt quantitative proteomics Infectious and parasitic diseases RC109-216
spellingShingle	newcastle disease virus matrix protein nuclear localization signal nucleocytoplasmic trafficking tmt quantitative proteomics Infectious and parasitic diseases RC109-216 Zhiqiang Duan Chao Yuan Yifan Han Lei Zhou Jiafu Zhao Yong Ruan Jiaqi Chen Mengmeng Ni Xinqin Ji TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
description	Nuclear localization of cytoplasmic RNA virus proteins mediated by intrinsic nuclear localization signal (NLS) plays essential roles in successful virus replication. We previously reported that NLS mutation in the matrix (M) protein obviously attenuates the replication and pathogenicity of Newcastle disease virus (NDV), but the attenuated replication mechanism remains unclear. In this study, we showed that M/NLS mutation not only disrupted M’s nucleocytoplasmic trafficking characteristic but also impaired viral RNA synthesis and transcription. Using TMT-based quantitative proteomics analysis of BSR-T7/5 cells infected with the parental NDV rSS1GFP and the mutant NDV rSS1GFP-M/NLSm harboring M/NLS mutation, we found that rSS1GFP infection stimulated much greater quantities and more expression changes of differentially expressed proteins involved in host cell transcription, ribosomal structure, posttranslational modification, and intracellular trafficking than rSS1GFP-M/NLSm infection. Further in-depth analysis revealed that the dominant nuclear accumulation of M protein inhibited host cell transcription, RNA processing and modification, protein synthesis, posttranscriptional modification and transport; and this kind of inhibition could be weakened when most of M protein was confined outside the nucleus. More importantly, we found that the function of M protein in the cytoplasm effected the inhibition of TIFA expression in a dose-dependent manner, and promoted NDV replication by down-regulating TIFA/TRAF6/NF-κB-mediated production of cytokines. It was the first report about the involvement of M protein in NDV immune evasion. Taken together, our findings demonstrate that NDV replication is closely related to the nucleocytoplasmic trafficking of M protein, which accelerates our understanding of the molecular functions of NDV M protein.
format	article
author	Zhiqiang Duan Chao Yuan Yifan Han Lei Zhou Jiafu Zhao Yong Ruan Jiaqi Chen Mengmeng Ni Xinqin Ji
author_facet	Zhiqiang Duan Chao Yuan Yifan Han Lei Zhou Jiafu Zhao Yong Ruan Jiaqi Chen Mengmeng Ni Xinqin Ji
author_sort	Zhiqiang Duan
title	TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
title_short	TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
title_full	TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
title_fullStr	TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
title_full_unstemmed	TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
title_sort	tmt-based quantitative proteomics analysis reveals the attenuated replication mechanism of newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/39168f0e1b27410e8d645f0c2dea02d4
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TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein

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