Induction of sialyl-Lex expression by herpes simplex virus type 1 is dependent on viral immediate early RNA-activated transcription of host fucosyltransferase genes.
We have previously shown that varicella-zoster virus (VZV) and cytomegalovirus (CMV) infection of diploid human fibroblasts (HEL) results in neo-expression of Lewis antigens sialyl Lewis x (sLe(x)) and Lewis y (Le(y)), respectively, after transcriptional activation of different combinations of dormant human fucosyltransferase genes (FUT1, FUT3, FUT5, and FUT6), whose gene products are responsible for the synthesis of Le antigens. Here, we show that herpes simplex virus type 1 (HSV-1) also induces sLe(x) expression dependent on induction of FUT3, FUT5, and FUT6 transcription in infected cells. HSV-1 induction of FUT5 was subsequently used as a model system for analyzing the mechanism of viral activation of dormant fucosyltransferase genes. We show that this is a rapid process, which gives rise to elevated FUT5 RNA levels already at 90 min postinfection. Augmented FUT5 transcription was found to be dependent on transcription of viral genes, but not dependent on the immediate early proteins ICP0 and ICP4, as demonstrated by experiments with HSV-1 mutants defective in expression of these genes. Augmented FUT5 transcription takes place in cycloheximide-treated HSV-1-infected cells, suggesting a more direct role for IE viral RNA during activation of cellular FUT5.
Nyström
Kristina
K
Department of Virology, University of Gothenburg, Gothenburg, Sweden.
Nordén
Rickard
R
Muylaert
Isabella
I
Elias
Per
P
Larson
Göran
G
Olofsson
Sigvard
S
D002460:Cell Line; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis*; D009154:Mutation; D009844:Oligosaccharides / Q000096:biosynthesis*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D015533:Transcriptional Activation
D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D012367:RNA, Viral; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases