Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription

doi:10.1128/JVI.00279-17

IOCAS-IR > 实验海洋生物学重点实验室

	Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription
	Ke, Qi 1,5; Weaver, Wade 1; Pore, Adam 1; Gorgoglione, Bartolomeo 1; Wildschutte, Julia Halo 1,6; Xiao, Peng 2,7; Shepherd, Brian S.3; Spear, Allyn 3; Malathi, Krishnamurthy 1; Stepien, Carol A.4; Vakharia, Vikram N.2; Leaman, Douglas W.1
	2017-10-01
发表期刊	JOURNAL OF VIROLOGY
卷号	91 期号:19
文章类型	Article
摘要	Viral hemorrhagic septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the Northern Hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral gene expression. By systematically screening each of the six VHSV structural and nonstructural genes, we identified matrix protein (M) as the virus' most potent antihost protein. Only M of VHSV genotype IV sublineage b (VHSV-IVb) suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner. M also suppressed the constitutively active simian virus 40 (SV40) promoter and globally decreased cellular RNA levels. Chromatin immunoprecipitation (ChIP) studies illustrated that M inhibited RNA polymerase II (RNAP II) recruitment to gene promoters and decreased RNAP II C-terminal domain (CTD) Ser2 phosphorylation during VHSV infection. However, transcription directed by RNAP I to III was suppressed by M. To identify regions of functional importance, M proteins from a variety of VHSV strains were tested in cell-based transcriptional inhibition assays. M of a particular VHSV-Ia strain, F1, was significantly less potent than IVb M at inhibiting SV40/ luciferase (Luc) expression yet differed by just 4 amino acids. Mutation of D62 to alanine alone, or in combination with an E181-to-alanine mutation (D62A E181A), dramatically reduced the ability of IVb M to suppress host transcription. Introducing either M D62A or D62A E181A mutations into VHSV-IVb via reverse genetics resulted in viruses that replicated efficiently but exhibited less cytotoxicity and reduced anti-transcriptional activities, implicating M as a primary regulator of cytopathicity and host transcriptional suppression.
关键词	Mavs Matrix Protein Vhsv Transcriptional Inhibition
DOI	10.1128/JVI.00279-17
收录类别	SCI
语种	英语
WOS记录号	WOS:000410261600001
引用统计	被引频次：30[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
版本	出版稿
条目标识符	http://ir.qdio.ac.cn/handle/337002/143164
专题	实验海洋生物学重点实验室
作者单位	1.Univ Toledo, Dept Biol Sci, 2801 W Bancroft St, Toledo, OH 43606 USA 2.Univ Maryland Baltimore Cty, Inst Marine & Environm Technol, Baltimore, MD 21228 USA 3.Univ Wisconsin, Sch Freshwater Sci, USDA ARS, Milwaukee, WI 53201 USA 4.NOAA, Pacific Marine Environm Lab, 7600 Sand Point Way Ne, Seattle, WA 98115 USA 5.Univ North Carolina Chapel Hill, Chapel Hill, NC USA 6.Bowling Green State Univ, Bowling Green, OH 43403 USA 7.Chinese Acad Sci, Inst Oceanol, Qingdao, Peoples R China
推荐引用方式 GB/T 7714	Ke, Qi,Weaver, Wade,Pore, Adam,et al. Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription[J]. JOURNAL OF VIROLOGY,2017,91(19).
APA	Ke, Qi.,Weaver, Wade.,Pore, Adam.,Gorgoglione, Bartolomeo.,Wildschutte, Julia Halo.,...&Leaman, Douglas W..(2017).Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription.JOURNAL OF VIROLOGY,91(19).
MLA	Ke, Qi,et al."Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription".JOURNAL OF VIROLOGY 91.19(2017).

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