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

Maki Kamakura,Yukihiro Nishiyama,Hiroshi Kimura,Fumi Goshima,Chenhong Luo

doi:10.1186/1743-422x-8-257

Abstract

BackgroundHerpes 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.ResultsINSM1 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.ConclusionsThe results suggest that INSM1 up-regulation plays a positive role in HSV-1 replication, probably by binding to the ICP0 promoter.

Highlights

Herpes simplex viruses (HSVs) rapidly shut off macromolecular synthesis in host cells
While US3 is not essential for viral replication in vitro, the protein kinases encoded by the US3 genes of Herpes simplex virus types 1 (HSV-1) and HSV-2 have been shown to play important roles in various aspects of viral replication and pathogenicity, including regulation of apoptosis and signal transduction and virion maturation [20,21,22,23,24]
Our microarray analysis showed that the level of insulinoma-associated 1 (INSM1) mRNAs increased by at least 400-fold 9 h after infection in HSV-infected cells compared with mock-infected cells

Summary

Introduction

Herpes simplex viruses (HSVs) rapidly shut off macromolecular synthesis in host cells. 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. Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are large DNA viruses with genomes consisting of at least 74 genes [1], which are classified into four groups with respect to their order of expression on the entry of HSV into the host cell. Immediate early (IE) genes are transcribed without prior viral protein synthesis. Genes are expressed before the onset of viral DNA synthesis and require IE gene expression. HSV infection markedly affects expression of host cell genes.

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