title: Inhibition of protein deacetylation augments herpes simplex virus type 1-activated transcription of host fucosyltransferase genes associated with virus-induced sLex expression.
abstract: Herpes simplex virus type 1 induces expression of the selectin ligand sialyl Lewis X in infected cells by activating transcription of three normally silent host glycosyltransferase genes, FUT3, FUT5, and FUT6, a process that is initiated by binding of viral RNA to cellular protein kinase R. We investigated the involvement of protein deacetylation and promoter methylation in viral activation of host FUT genes by analysing the effects of appropriate inhibitors on the transcription rates of the FUT genes in virus-infected cells. The histone deacetylase inhibitor trichostatin A augmented the viral activation of FUT transcription, whereas inhibition of DNA methylation did not affect transcription of these genes. The trichostatin A enhancement did not involve interference with expression of viral late genes or viral DNA replication. Thus, the virus-activated FUT genes are at least partially suppressed by deacetylation of histones or other regulatory proteins in uninfected HEL cells, whereas promoter methylation is a less important factor.
authors.affiliation: Department of Virology, University of Gothenburg, Guldhedsgatan 10B, Göteborg, Sweden.
authors.forename: Rickard
authors.initials: R
authors.lastname: Nordén
authors.forename: Kristina
authors.initials: K
authors.lastname: Nyström
authors.forename: Sigvard
authors.initials: S
authors.lastname: Olofsson
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D019175:DNA Methylation; D005647:Fucosyltransferases / Q000096:biosynthesis*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D016256:Lewis X Antigen / Q000096:biosynthesis*; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D008954:Models, Biological; D014158:Transcription, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016256:Lewis X Antigen; C012589:trichostatin A; D008780:Methyltransferases; D005647:Fucosyltransferases; C418611:alpha3-fucosyltransferase V; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase; C515956:FUT6 protein, human; D006655:Histone Deacetylases