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Herpes simplex virus type Ⅰ (HSV-1) is a double-stranded DNA virus with a complicated structure and a specific role in the cascade effect in gene transcription regulation. HSV-1 shows characteristics at different levels in its interaction with cells [2, 11], such as the influence of HSV-1 infection-related protein on viral replication function—the working mechanism of which has gradually become one of the key research fields in molecular biology [6, 10]. In our previous studies, we conducted more detailed research on related proteins induced by HSV-1 infection in human fibroblasts using mRNA differential display technology and protein 2D differential technology [7, 8], and obtained a number of HSV-1 infection-related proteins [9, 13]. Once such protein was HTRP (human transcription regulator protein) which is associated with transcriptional regulation and interacts with part of the transcriptional co-repressor mSin3A complex SAP30 (mSin3A Association Protein) to promote HSV-1 infection which leads to cell death [5]. This finding suggested that HTRP may have a direct or indirect impact on HSV-1 transcriptional regulation as an HSV-1 infection-related protein, possibly through some specific intracellular biological pathway. Our research could potentially provide a direct basis for helping to understand the biological significance of the interaction between HSV-1 and host cells, reflected in the regulation and transcription of viral genes through an intracellular protein modification system. On this basis, further experiments were designed to analyze the transcriptional regulation mechanism of different HSV-1 genes by HTRP. The results showed that HTRP's influence on the transcription regulation process of HSV-1 was simulated by promoting deacetylation enzyme HDAC activity, which regulates viral gene transcription through HSV-1 gene chromatin reunion/deconstruction. The results provide some insight into the biological characteristics of using the intracellular chromatin reunion/deconstruction mechanism to achieve different pathological results in the process of HSV-1 infection. In addition, a relevant research basis would be provided for understanding the interaction between HSV-1 and its host cells from the view of cellular molecule modifying enzymes.
Transcriptional Regulation by HSV-1 Induced HTRP via Acetylation System
- Received Date: 07 May 2010
- Accepted Date: 28 July 2010
Abstract: The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells. HTRP was found to interact with SAP30 (mSin3A Association Protein), one of the components of co-repressor complex mSin3A, which is part of the deacetylation transfer enzyme HDAC. To reveal the biological significance of the interaction between HTRP and SAP30, real- time PCR and a dual-luciferase detecting system was used. The results indicate that HTRP could inhibit the transcription of a viral promoter, whose interaction with SAP30 synergistically affects transcriptional inhibition of the viral genes, and is related to HDAC enzyme activity. ChIP experiments demonstrate that HTRP could promote HDAC activity by increasing the deacetylation level of lysine 14 and lysine 9 in histone H3.