Fhyroid hormone controls the gene expression of HSV-1 .AT and ICPO in neuronal cells

• Published in: Cell research no. 5; pp. 587 - 598
• Main Author: Gautam R Bedadala Rajeswara C Pirmoji Jayavardhana R Palem1, Shao-Chung V Hsia Shao-Chung V Hsia Jayavardhana R Palem
• Format: Journal Article
• Language: English
• Published: 2010
• Subjects: HSV; 单纯疱疹病毒; 基因表达; 染色质免疫沉淀; 激素控制; 甲状腺激素受体; 神经细胞; 转录因子
• ISSN: 1001-0602; 1748-7838

Various factors/pathways including hormonal regulation have been suggested to control herpes simplex virus type 1 （HSV-1） latency and reactivation. Our computer analysis identified a DNA repeat containing thyroid hormoneresponsive elements （TRE） in the regulatory region of HSV-1 latency-associated transcript （LAT）. Thyroid hormone （triiodothyronine, T3） functions via its receptor TR （thyroid hormone receptor）, a transcription factor. Present study investigated the roles of TR and T3 in HSV-1 gene expression using cultured neuoroblastoma cell lines. We demonstrated that liganded TR activated LAT transcription, but repressed infected cell protein no. 0 （ICP0） transcription in the presence of LAT TRE. Chromatin immunoprecipitation （CHIP） assays showed that TRs were recruited to LAT TREs independently of T3 and hyperacetylated H4 was associated with the LAT promoter that was transcriptionally active. In addition, ChIP results showed that the chromatin insulator protein CCCTC-binding factor was enriched at the LAT TREs in the presence of TR and T3. In addition, the BRG1 chromatin remodeling complex is found to participate in the T3/TR-mediated LAT activation since overexpression of BRG1 enhanced the LAT transcription and the dominant-negative mutant K785R abolished the activation. This is the first report revealing that TR elicits epigenetic regulation on HSV-1 ICP0 expression in neuronal cells and could have a role in the complex processes of HSV-1 latency/reactivation.