Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: Viral block to the accumulation of antiviral mRNAs
Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: Viral block to the accumulation of antiviral mRNAs
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DOI：
10.1128/jvi.75.24.12319-12330.2001
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发表时间：
2001-12-01
影响因子：
5.4
通讯作者：
Shenk, T
中科院分区：
文献类型：
--
作者：
Browne, EP;Wing, B;Shenk, T
应用基因芯片技术分析人巨细胞病毒（HCMV）感染对细胞mRNA积累的影响。在感染人二倍体成纤维细胞后48小时的时间过程中，发现1，425种细胞mRNA在至少两个连续时间点上调或下调三倍或更多。几类基因受到显着影响，包括干扰素反应基因、细胞周期调节因子、细胞凋亡调节因子、炎症途径基因和免疫调节因子。上调或下调的mRNA数量在整个时间过程中大致相等。然而，在感染后的第一个8小时，上调的mRNA的数量显着低于下调的mRNA的数量。通过分析放线菌酮存在下感染的细胞的mRNA表达谱，发现在蛋白质合成不存在的情况下，最少有25种mRNA被HCMV调节。这些包括由少量干扰素应答基因编码的mRNA，以及β干扰素本身。将巨细胞病毒感染的细胞中的细胞mRNA水平与UV灭活病毒感染的细胞中的水平进行比较。灭活的病毒引起大量mRNA的上调，其中许多编码具有抗病毒作用的蛋白质，如干扰素应答基因和促炎细胞因子。这些数据表明，一种或多种新合成的病毒基因产物阻断了由HCMV结合和进入触发的抗病毒途径的诱导。
The effect of human cytomegalovirus (HCMV) infection on cellular mRNA accumulation was analyzed by gene chip technology. During a 48-h time course after infection of human diploid fibroblasts, 1,425 cellular mRNAs were found to be up-regulated or down-regulated by threefold or greater in at least two consecutive time points. Several classes of genes were prominently affected, including interferon response genes, cell cycle regulators, apoptosis regulators, inflammatory pathway genes, and immune regulators. The number of mRNAs that were up-regulated or down-regulated were roughly equal over the complete time course. However, for the first 8 h after infection, the number of up-regulated mRNAs was significantly less than the number of down-regulated mRNAs. By analyzing the mRNA expression profile of cells infected in the presence of cycloheximide, it was found that a minimum of 25 mRNAs were modulated by HCMV in the absence of protein synthesis. These included mRNAs encoded by a small number of interferon-responsive genes, as well as beta interferon itself, Cellular mRNA levels in cytomegalovirus-infected cells were compared to the levels in cells infected with UV-inactivated virus. The inactivated virus caused the up-regulation of a much greater number of mRNAs, many of which encoded proteins with antiviral roles, such as interferon-responsive genes and proinflammatory cytokines. These data argue that one or more newly synthesized viral gene products block the induction of antiviral pathways that are triggered by HCMV binding and entry.