title: A Novel Thyroid Hormone Mediated Regulation of HSV-1 Gene Expression and Replication is Specific to Neuronal Cells and Associated with Disruption of Chromatin Condensation.
abstract: Previously we showed that thyroid hormone (T3) regulated the Herpes Simplex Virus Type -1 (HSV-1) gene expression and replication through its nuclear receptor TR via histone modification and chromatin remodeling in a neuroblastoma cell line neuro-2a cells (N2a). This observation suggested that T3 regulation may be neuron-specific and have implication in HSV-1 latency and reactivation. In this study, our in vitro latency/reactivation model demonstrated that removal of T3 can de-repress the HSV-1 replication and favor reactivation. Transfection studies and infection assays indicated that HSV-1 thymidine kinase (TK), a key viral gene during reactivation, was repressed by TR/T3 in cells with neuronal origin but not in non-neuronal cells. Additional studies showed that RCC1 (Regulator of Chromosome Condensation 1) was sequestered but efficiently detected upon viral infection in N2a cells. Western blot analyses indicated that addition of T3 repressed the RCC1 expression upon infection. It is likely that diminution of RCC1 upon infection in neuronal cells under the influence of TR/T3 may lead to repression of viral replication/gene expression thus promote latency. Together these results demonstrated that TR/T3 mediated regulation is specific to neuronal cells and differential chromosome condensation may play a critical role in this process.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853 Maryland, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853 Maryland, United States.
authors.forename: Jay
authors.initials: J
authors.lastname: Palem
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853 Maryland, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Balish
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853 Maryland, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Figliozzi
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853 Maryland, United States.
authors.forename: Amakoe
authors.initials: A
authors.lastname: Ajavon
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853 Maryland, United States.
authors.forename: S Victor
authors.initials: SV
authors.lastname: Hsia
keywords: Chromosome; HSV-1; Latency; Neuron; Thyroid hormone