Inhibition of protein deacetylation augments herpes simplex virus type 1-activated transcription of host fucosyltransferase genes associated with virus-induced sLex expression
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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.
KeywordsGastric Cancer Cell Herpes Simplex Virus Type Immediate Early Zebularine Selectin Ligand
This work was supported by the Swedish Research Council (grant15283) and by grants from the LUA-ALF Foundation, Sahlgrenska University Hospital, Gothenburg. The authors acknowledge the Centre for Cellular Imaging at Gothenburg University for use of imaging equipment and for the support from the staff.
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