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

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Endoplasmic reticulum (ER) stress is implicated in herpes simplex virus type 1 (HSV-1) replication.
• Tauroursodeoxycholic acid (TUDCA) is known to protect liver function by mitigating ER stress and apoptosis.

Purpose of the Study:

• To investigate the effect of TUDCA on HSV-1 replication in HEC-1-A cells.
• To elucidate the mechanisms by which TUDCA influences ER stress pathways during HSV-1 infection.

Main Methods:

• HEC-1-A cells were infected with HSV-1 in the presence of varying concentrations of TUDCA.
• Viral replication and multiplication were assessed.
• Expression levels and activation states of key ER stress pathway components (ATF6, PERK, IRE1α) were analyzed.

Main Results:

• TUDCA significantly inhibited HSV-1 replication and multiplication in a dose-dependent manner.
• TUDCA alleviated the inhibition of the Activating Transcription Factor 6 (ATF6) pathway.
• TUDCA partially enhanced the Protein Kinase RNA-like ER Kinase (PERK) pathway while significantly repressing the Inositol-Requiring Protein 1α (IRE1α) pathway.

Conclusions:

• TUDCA demonstrates antiviral activity against HSV-1 by modulating ER stress responses.
• The findings suggest TUDCA as a potential therapeutic agent for managing HSV-1 infections through its influence on cellular stress pathways.