Overexpression of thyroid hormone receptor β1 altered thyroid hormone-mediated regulation of herpes simplex virus-1 replication in differentiated cells.

Thyroid hormone (T3) has been suggested to play a role in herpes simplex virus 1 (HSV-1) replication. It was previously reported that HSV-1 replication was suppressed by T3 in mouse neuroblastoma cells overexpressing thyroid hormone receptor β1 (TRβ1). Using a human neuro-endocrine cells LNCaP differentiated by androgen deprivation, HSV-1 replication was active but decreased by T3 at very low moi, probably due to low copy of TRβ1. In this study, a recombinant HSV-1 was constructed expressing TRβ1 (HSV-1/TRβ1). Infection of Vero cells (very little TRβ1 expression) with HSV-1/TRβ1 exhibited increased replication in the presence of T3 compared to the counterpart without TRβ1 overexpression. Interestingly, HSV-1/TRβ1 infection of differentiated LNCaP cells showed strong suppression of viral replication by T3 and the removal of hormone did not fully reversed the suppression as was observed in parent virus. Quantitative analyses indicated that ICP0 expression was blocked using HSV-1/TRβ1 for infection during T3 washout, suggesting that overexpression of TRβ1 is likely to delay its inhibitory effect on viral gene expression. Together these results emphasized the importance of TRβ1 in the regulation of HSV-1 replication in differentiated environment with neuronal phenotype.