Department of Infectious Diseases/Clinical Virology, Institute of Biomedicine, University of Gothenburg, Sahlgrenska Academy, Guldhedsgatan 10B, SE-413 46 Gothenburg, Sweden.
Glycobiology. 2017 Nov 1;27(11):999-1005. doi: 10.1093/glycob/cwx079.
Herpes simplex virus type 1 has the ability to induce expression of a human gene cluster located on chromosome 19 upon infection. This gene cluster contains three fucosyltransferases (encoded by FUT3, FUT5 and FUT6) with the ability to add a fucose to an N-acetylglucosamine residue. Little is known regarding the transcriptional activation of these three genes in human cells. Intriguingly, herpes simplex virus type 1 activates all three genes simultaneously during infection, a situation not observed in uninfected tissue, pointing towards a virus specific mechanism for transcriptional activation. The aim of this study was to define the underlying mechanism for the herpes simplex virus type 1 activation of FUT3, FUT5 and FUT6 transcription. The transcriptional activation of the FUT-gene cluster on chromosome 19 in fibroblasts was specific, not involving adjacent genes. Moreover, inhibition of NFκB signaling through panepoxydone treatment significantly decreased the induction of FUT3, FUT5 and FUT6 transcriptional activation, as did siRNA targeting of p65, in herpes simplex virus type 1 infected fibroblasts. NFκB and p65 signaling appears to play an important role in the regulation of FUT3, FUT5 and FUT6 transcriptional activation by herpes simplex virus type 1 although additional, unidentified, viral factors might account for part of the mechanism as direct interferon mediated stimulation of NFκB was not sufficient to induce the fucosyltransferase encoding gene cluster in uninfected cells.
单纯疱疹病毒 1 型在感染时具有诱导位于 19 号染色体上的人类基因簇表达的能力。该基因簇包含三个岩藻糖基转移酶（由 FUT3、FUT5 和 FUT6 编码），能够在 N-乙酰葡萄糖胺残基上添加一个岩藻糖。关于这些基因在人细胞中的转录激活知之甚少。有趣的是，单纯疱疹病毒 1 在感染过程中同时激活这三个基因，而在未感染的组织中未观察到这种情况，这表明存在病毒特异性的转录激活机制。本研究旨在确定单纯疱疹病毒 1 激活 FUT3、FUT5 和 FUT6 转录的潜在机制。成纤维细胞中 19 号染色体上 FUT 基因簇的转录激活是特异性的，不涉及相邻基因。此外，通过 panepoxydone 处理抑制 NFκB 信号通路显著降低了 FUT3、FUT5 和 FUT6 转录激活的诱导，而针对 p65 的 siRNA 靶向治疗也是如此，在单纯疱疹病毒 1 感染的成纤维细胞中。NFκB 和 p65 信号通路似乎在单纯疱疹病毒 1 调节 FUT3、FUT5 和 FUT6 转录激活中发挥重要作用，尽管其他未识别的病毒因素可能部分解释了该机制，因为直接干扰素介导的 NFκB 刺激不足以诱导未感染细胞中岩藻糖基转移酶编码基因簇的表达。
