Virus-induced transcriptional activation of host FUT genes associated with neo-expression of Ley in cytomegalovirus-infected and sialyl-Lex in varicella-zoster virus-infected diploid human cells.

ABSTRACT

Cell surface carbohydrate structures including sialyl-Lewis X (sLe(x)) and Lewis Y (Le(y)) are important ligands in normal and malignant tissues. The aim here was to determine the possible influence on the expression of such antigens by two viruses varicella-zoster virus (VZV) and cytomegalovirus (CMV) involved in persistent infections of humans. We found that infection of human diploid fibroblasts with both viruses resulted in transcriptional activation of several fucosyltransferase (FUT) genes that were either dormant or expressed at low levels in uninfected cells. Both viruses induced FUT3, FUT5, and FUT6, encoding alpha1,3- and/or alpha1,4-specific fucosyltransferases. CMV, but not VZV, induced transcription of FUT1 (encoding an alpha1,2-specific fucosyltransferase), FUT7, and FUT9. The changes in transcription of FUT genes were expectedly associated with expression of Le(y) in CMV-infected cells and sLe(x) in the VZV-infected fibroblasts although no expression of these antigens was observed in uninfected cells. One major explanation for this difference between CMV- and VZV-infected cells was that CMV, but not VZV, induced expression of FUT1, necessary for Le(y) expression. The induced carbohydrate antigens in CMV- and VZV-infected cells could be of significance for virus spread and possible escape from immune responses.