Thyroid hormone controls the gene expression of HSV-1 LAT and ICP0 in neuronal cells

• Published in: Cell research Vol. 20; no. 5; pp. 587 - 598
• Main Authors: Bedadala, Gautam R, Pinnoji, Rajeswara C, Palem, Jayavardhana R, Hsia, Shao-Chung V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2010; Nature Publishing Group
• Subjects: 631/208/200; 631/326/596/1553; 631/378/2571/1696; 631/45/776/1180; Animals; Base Sequence; Biomedical and Life Sciences; Cell Biology; Cell Line, Tumor; Chromatin - metabolism; Deoxyribonucleic acid; DNA; Gene Expression Regulation, Viral; Herpes Simplex - genetics; Herpes Simplex - metabolism; Herpes simplex virus 1; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - metabolism; Life Sciences; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Sequence Data; Neurons - metabolism; Neurons - virology; original-article; Receptors, Thyroid Hormone - metabolism; Thyroid; Transcription, Genetic; Triiodothyronine - metabolism; HSV-1; thyroid hormone; transcription; latency; ICP0; chromatin; LAT
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2010.50

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 hormone-responsive elements (TRE) in the regulatory region of HSV-1 latency-associated transcript (LAT). Thyroid hormone (triiodothyronine, T 3 ) functions via its receptor TR (thyroid hormone receptor), a transcription factor. Present study investigated the roles of TR and T 3 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 T 3 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 T 3 . In addition, the BRG1 chromatin remodeling complex is found to participate in the T 3 /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.