SUMOylation of pseudorabies virus thymidine kinase regulates its nuclear localization and facilitates neuronal replication and reactivation.

SUMOylation of PRV thymidine kinase at lysines K242 and K267 is essential for its nuclear localization, neuronal replication, and viral reactivation, impacting pathogenesis.

• Why it matters: Understanding how viral proteins are regulated post-translationally can reveal new targets for controlling herpesvirus infections, especially in neurons where latency and reactivation occur.
• What they did: The study identified PRV thymidine kinase as a substrate for SUMO modification, with key sites at K242 and K267, and examined its effects on localization, replication, and reactivation using cell and mouse models.
• The result: Disruption of TK SUMOylation impairs nuclear localization, reduces neuronal reactivation, and attenuates PRV pathogenicity in mice, highlighting SUMOylation as a potential therapeutic target.