title: 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 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.
authors.affiliation: Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe College of Pharmacy, Monroe, LA 71209, USA.
authors.forename: Gautam R
authors.initials: GR
authors.lastname: Bedadala
authors.forename: Rajeswara C
authors.initials: RC
authors.lastname: Pinnoji
authors.forename: Jayavardhana R
authors.initials: JR
authors.lastname: Palem
authors.forename: Shao-Chung V
authors.initials: SC
authors.lastname: Hsia
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000235:genetics* / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D002843:Chromatin; D035683:MicroRNAs; D011988:Receptors, Thyroid Hormone; C477253:latency associated transcript, herpes simplex virus-1; D014284:Triiodothyronine
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