Overview

• Herpes simplex virus type 1 uses its viral uracil-DNA glycosylase (vUNG) to remove APOBEC1-induced uracils and evade intrinsic antiviral defenses.
• Researchers found that phosphorylation of vUNG is essential for its enzymatic activation and ability to counter APOBEC1 in neural tissue.
• An adeno-associated virus vector engineered to express a uracil glycosylase inhibitor (UGI) effectively neutralizes vUNG and reactivates APOBEC1-mediated DNA editing.
• In mouse models, pre-treatment with the AAV-UGI vector dramatically reduced HSV-1 replication in the brain and averted fatal encephalitis.
• The protective effect requires APOBEC1 and underscores the promise of host-directed therapies targeting viral DNA repair across neurotropic infections.