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

Abstract

Various factors/pathways including hormonal regulation have been suggested to control HSV-1 latency and reactivation. Our computer analysis identified a DNA repeat containing thyroid hormone response elements (TRE) in the regulatory region of HSV-1 LAT. Thyroid hormone (T3) exerts its function via its receptor (TR), a transcriptional factor. Present study investigated the roles of TR and T3 on HSV-1 gene expression using cultured neuoroblastoma cell lines. We demonstrated that liganded TR activated LAT transcription but repressed ICP0 transcription in the presence of LAT TRE. The chromatin immunoprecipitation (ChIP) assays showed that TRs were recruited to LAT TREs independently of T3 and hyperacetylated H4 was associated with promoters that were transcriptionally active. In addition, ChIP results showed that a chromatin insulator protein CTCF was enriched at the LAT TREs in the presence of TR and T3. In addition, chromatin remodeling factor BRG1 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 exerted epigenetic regulation on HSV-1 ICP0 expression in neuronal cells and could have a role in the complex processes of HSV-1 latency/reactivation.