ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication

• DOI: 10.1371/journal.ppat.1012452
• Publication Date: 2025-04-08T18:35:58Z
• Authors: Adwait Parchure; Mia Cesarec; Antonija Braut; Robert Kolman; Vlatka Ivanišević; Marina Čunko; Slađana Bursać; Richard de Reuver; Antonija J. Begonja; Umberto Rosani; Siniša Volarević; Jonathan Maelfait; Igor Jurak
• Keywords: Protein kinase R; RNA Silencing; Intrinsic immunity; Stress granule

Adenosine deaminase acting on dsRNA 1 (ADAR1) catalyzes the deamination of adenosines to inosines in double-stranded RNAs (dsRNA) and regulates innate immunity by preventing hyperactivation cytosolic sensors such as MDA5, PKR or ZBP1. ADAR1 has been shown exert pro- antiviral, editing-dependent editing-independent functions viral infections, but little is known about its function herpesvirus replication. We now demonstrate that herpes simplex virus (HSV-1) hyperactivates absence ADAR1, resulting eIF2α mediated translational arrest reduced Silencing inhibition downstream effectors (ICP34.5) pharmacological (ISRIB) inhibitors rescues replication ADAR1-deficient cells. Upon infection, p150 interacts with prevents hyperactivation. Our findings an important proviral factor raises activation threshold for immunity.