PMID:12663771

Citation	Ahmed, M, McKenzie, MO, Puckett, S, Hojnacki, M, Poliquin, L and Lyles, DS (2003) Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis. J. Virol. 77:4646-57
Abstract	The vesicular stomatitis virus (VSV) matrix (M) protein plays a major role in the virus-induced inhibition of host gene expression. It has been proposed that the inhibition of host gene expression by M protein is responsible for suppressing activation of host interferon gene expression. Most wild-type (wt) strains of VSV induce little if any interferon gene expression. Interferon-inducing mutants of VSV have been isolated previously, many of which contain mutations in their M proteins. However, it was not known whether these M protein mutations were responsible for the interferon-inducing phenotype of these viruses. Alternatively, mutations in other genes besides the M gene may enhance the ability of VSV to induce interferons. These hypotheses were tested by transfecting cells with mRNA expressing wt and mutant M proteins in the absence of other viral components and determining their ability to inhibit interferon gene expression. The M protein mutations were the M51R mutation originally found in the tsO82 and T1026R1 mutant viruses, the double substitution V221F and S226R found in the TP3 mutant virus, and the triple substitution E213A, V221F, and S226R found in the TP2 mutant virus. wt M proteins suppressed expression of luciferase from the simian virus 40 promoter and from the beta interferon (IFN-beta) promoter, while M proteins of interferon-inducing viruses were unable to inhibit luciferase expression from either promoter. The M genes of the interferon-inducing mutants of VSV were incorporated into the wt background of a recombinant VSV infectious cDNA clone. The resulting recombinant viruses were tested for their ability to activate interferon gene expression and for their ability to inhibit host RNA and protein synthesis. Each of the recombinant viruses containing M protein mutations induced expression of a luciferase reporter gene driven by the IFN-beta promoter and induced production of interferon bioactivity more effectively than viruses containing wt M proteins. Furthermore, the M protein mutant viruses were defective in their ability to inhibit both host RNA synthesis and host protein synthesis. These data support the idea that wt M protein suppresses interferon gene expression through the general inhibition of host RNA and protein synthesis.
Links	PubMed PMC152115
Keywords	Animals; Cricetinae; Gene Expression Regulation; HeLa Cells; Humans; Interferon-beta/genetics; Interferon-beta/metabolism; Mutation; Promoter Regions, Genetic; Proteins/genetics; Proteins/metabolism; RNA/genetics; RNA/metabolism; Transfection; Tumor Cells, Cultured; Vesicular stomatitis Indiana virus/genetics; Vesicular stomatitis Indiana virus/pathogenicity; Viral Matrix Proteins/genetics; Viral Matrix Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
9RHAB:S5TDC0	involved_in	GO:0039501: suppression by virus of host type I interferon production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
9RHAB:S5TDC0	involved_in	GO:0039653: suppression by virus of host transcription	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
9RHAB:S5TDC0	involved_in	GO:0039604: suppression by virus of host translation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
9RHAB:S5TDC0		GO:0039657: suppression by virus of host gene expression	ECO:0000315:		P		Fig 1D: cells were transfected with SV40-promoter-luciferase-reporter plasmid and wildtype or mutant M mRNA - wildtype inhibited luciferase expression, mutants didn't Fig. 1C: expression of HR wildtype strain and mutants TP2 and TP3 were similar, meaning that decreased luciferase expression resulted from M protein mutations, not decreased M expression	complete CACAO 9986
9RHAB:S5TDC0		GO:0039501: suppression by virus of host type I interferon production	ECO:0000315:		P		Fig. 2: cells were transfected with IFN-beta-promoter-luciferase-reporter plasmid and wildtype or mutant M mRNA - wildtype inhibited luciferase expression, mutants didn't	complete CACAO 9989
9RHAB:S5TDC0		GO:0039653: suppression by virus of host transcription	ECO:0000315:		P		Fig. 6: cells were infected with wildtype or mutant viruses, wildtype inhibited RNA synthesis more than mutant	complete CACAO 10010
9RHAB:S5TDC0		GO:0039604: suppression by virus of host translation	ECO:0000315:		P		Fig. 7B: cells were infected with wildtype or mutant viruses, wildtype inhibited host cell protein synthesis more than mutant	complete CACAO 10022

References

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