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病毒诱导宿主FUT基因的转录激活,这与巨细胞病毒感染的二倍体人类细胞中Ley的新表达以及水痘带状疱疹病毒感染的二倍体人类细胞中唾液酸化Lex的新表达相关。

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.

作者信息

Nyström Kristina, Grahn Ammi, Lindh Magnus, Brytting Maria, Mandel Ulla, Larson Göran, Olofsson Sigvard

机构信息

Department of Virology, University of Göteborg, Göteborg, Sweden.

出版信息

Glycobiology. 2007 Apr;17(4):355-66. doi: 10.1093/glycob/cwl083. Epub 2007 Jan 3.

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.

摘要

包括唾液酸化路易斯X(sLe(x))和路易斯Y(Le(y))在内的细胞表面碳水化合物结构是正常组织和恶性组织中的重要配体。本研究的目的是确定两种参与人类持续性感染的病毒——水痘带状疱疹病毒(VZV)和巨细胞病毒(CMV)对这类抗原表达可能产生的影响。我们发现,用这两种病毒感染人二倍体成纤维细胞会导致几种岩藻糖基转移酶(FUT)基因转录激活,这些基因在未感染的细胞中要么处于休眠状态,要么表达水平很低。两种病毒均诱导了编码α1,3-和/或α1,4-特异性岩藻糖基转移酶的FUT3、FUT5和FUT6。CMV(而非VZV)诱导了FUT1(编码α1,2-特异性岩藻糖基转移酶)、FUT7和FUT9的转录。FUT基因转录的变化预期与CMV感染细胞中Le(y)的表达以及VZV感染的成纤维细胞中sLe(x)的表达相关,尽管在未感染的细胞中未观察到这些抗原的表达。CMV感染细胞和VZV感染细胞之间这种差异的一个主要解释是,CMV(而非VZV)诱导了Le(y)表达所必需的FUT1的表达。CMV和VZV感染细胞中诱导产生的碳水化合物抗原可能对病毒传播以及可能逃避免疫反应具有重要意义。

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