单纯疱疹病毒诱导锌指转录因子 INSM1 的显著上调，该因子调节即刻早期蛋白 ICP0 的表达和定位。

Herpes simplex virus induces the marked up-regulation of the zinc finger transcriptional factor INSM1, which modulates the expression and localization of the immediate early protein ICP0.

机构信息

Department of Virology, Nagoya Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

出版信息

Virol J. 2011 May 25;8:257. doi: 10.1186/1743-422X-8-257.

BACKGROUND

Herpes simplex viruses (HSVs) rapidly shut off macromolecular synthesis in host cells. In contrast, global microarray analyses have shown that HSV infection markedly up-regulates a number of host cell genes that may play important roles in HSV-host cell interactions. To understand the regulatory mechanisms involved, we initiated studies focusing on the zinc finger transcription factor insulinoma-associated 1 (INSM1), a host cell protein markedly up-regulated by HSV infection.

RESULTS

INSM1 gene expression in HSV-1-infected normal human epidermal keratinocytes increased at least 400-fold 9 h after infection; INSM1 promoter activity was also markedly stimulated. Expression and subcellular localization of the immediate early HSV protein ICP0 was affected by INSM1 expression, and chromatin immunoprecipitation (ChIP) assays revealed binding of INSM1 to the ICP0 promoter. Moreover, the role of INSM1 in HSV-1 infection was further clarified by inhibition of HSV-1 replication by INSM1-specific siRNA.

CONCLUSIONS

The results suggest that INSM1 up-regulation plays a positive role in HSV-1 replication, probably by binding to the ICP0 promoter.

背景

单纯疱疹病毒（HSV）可迅速使宿主细胞中的大分子合成失活。相比之下，全基因组微阵列分析表明，HSV 感染显著上调了许多宿主细胞基因，这些基因可能在 HSV-宿主细胞相互作用中发挥重要作用。为了了解所涉及的调控机制，我们开始研究胰岛素瘤相关 1（INSM1）这一宿主细胞蛋白，它是 HSV 感染后显著上调的宿主细胞蛋白。

结果

在 HSV-1 感染的正常人表皮角质形成细胞中，INSM1 基因的表达在感染后 9 小时至少增加了 400 倍；INSM1 启动子活性也明显受到刺激。瞬时早期 HSV 蛋白 ICP0 的表达和亚细胞定位受 INSM1 表达的影响，染色质免疫沉淀（ChIP）实验显示 INSM1 与 ICP0 启动子结合。此外，通过 INSM1 特异性 siRNA 抑制 HSV-1 复制，进一步阐明了 INSM1 在 HSV-1 感染中的作用。