Glycobiology Advance Access published online on April 15, 2009
Glycobiology, doi:10.1093/glycob/cwp057
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Induction of sialyl-Lex expression by herpes simplex virus type 1 is dependent on viral immediate early RNA-activated transcription of host fucosyltransferase genes
1 Department of Virology
2 Department of Clinical Chemistry and Transfusion Medicine
3 Department of Medical Chemistry, University of Gothenburg, Gothenburg
* Corresponding author:, Dr. Sigvard Olofsson, Department of Virology, University of Gothenburg, Guldhedsgatan 10B, S-413 46 Göteborg, Phone +46 31 342 46 59, Fax +46 31 82 70 32, Email sigvard.olofsson{at}microbio.gu.se
Received on February 10, 2009; accepted on April 13, 2009
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 (sLex) and Lewis y (Ley), respectively, after transcriptional activation of different combinations of dormant human fucosyltransferase genes (FUT1, FUT3, FUT5, and FUT6), whose gene products are responsible for synthesis of Le antigens. Here, we show that herpes simplex virus type 1 (HSV-1) also induces sLex 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 minutes post infection. 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.
Key words: Herpes simplex virus / fucosyltransferase / sialyl-Lewis X / transcription / ICP0