TUDCA inhibits HSV-1 replication by the modulating unfolded protein response pathway

Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, was used to protect liver function through antiapoptosis or reducing endoplasmic reticulum stress (ER stress). Previous studies showed that ER stress was modulated by herpes simplex virus types 1 (HSV-1) infection to facilitate viral replication. Here, we investigated the effect of TUDCA on HSV-1 infection of HEC-1-A cells and showed that both replication and multiplication of the virus were inhibited by TUDCA in a dose dependent manner. Unfolded protein response was induced to deliver stress signals from ER to nucleus. We found that TUDCA alleviated activating transcription factor 6 branch inhibition, partially enhanced protein kinase RNA-like ER kinase pathway activation, and repressed inositol-requiring protein 1 alpha arm activation significantly in infected cells. The findings of this study suggest that TUDCA inhibits HSV-1 replication through ER stress pathway, which may provide a potential therapeutic strategy for HSV-1 infection.