Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9
Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9
复制标题
DOI：
10.1074/jbc.m608667200
复制
发表时间：
2007-03-16
影响因子：
4.8
通讯作者：
Kenney, Shannon C.
中科院分区：
文献类型：
--
作者：
Jones, Richard J.;Dickerson, Sarah;Kenney, Shannon C.
裂解性EB病毒（EBV）复制发生在分化的上皮细胞中，而不是未分化的上皮细胞中。视黄酸（RA）诱导上皮细胞分化。将视黄醇转化为其活性形式视黄酸需要视黄醇脱氢酶。在这里，我们表明，AGS胃癌细胞含有裂解形式的EBV感染增强表达的基因（DHRS9）编码的酶，介导的视黄醇转化为RA。在EBV阳性伯基特淋巴瘤细胞中诱导裂解性病毒感染后，DHRS9表达也增加。我们证明了EBV立即早期蛋白BZLF1通过直接DNA结合机制激活DHRS9启动子。此外，BZLF1在AGS细胞中的表达足以激活DHRS9基因表达，并增加视黄醇诱导RA应答基因CYP26A1的能力。在EBV感染的裂解形式期间产生RA可通过促进角质形成细胞分化来增强病毒复制。
Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS gastric carcinoma cells containing the lytic form of EBV infection have enhanced expression of a gene (DHRS9) encoding an enzyme that mediates conversion of retinol into RA. DHRS9 expression is also increased following induction of lytic viral infection in EBVpositive Burkitt lymphoma cells. We demonstrate that the EBV immediate-early protein, BZLF1, activates the DHRS9 promoter through a direct DNA binding mechanism. Furthermore, BZLF1 expression in AGS cells is sufficient to activate DHRS9 gene expression and increases the ability of retinol to induce the RA-responsive gene, CYP26A1. Production of RA during the lytic form of EBV infection may enhance viral replication by promoting keratinocyte differentiation.