Spatiotemporal regulation of Pseudorabies Virus Thymidine kinase UL23 by post-translational modification

Abstract

AbstractPost-translational modification plays a significant role in the interaction between viruses and their hosts. The pseudorabies virus (PRV) is a highly contagious herpesvirus that affects the central nervous system and respiratory tract of swine. However, the role of post-translational modifications, including Ubiquitination and SUMOylation, in host and PRV interplays is poorly understood. Here we examined the SUMO modification of PRV proteins and revealed that the PRV thymidine kinase UL23 can undergo SUMO modification. Bioinformatic analysis suggested four potential modification sites for UL23. Site-directed mutagenesis indicates that SUMO modification occurs at sites K242 and K267 as the wild type localizes in the nucleus while the mutants localize in the cytoplasm. Subsequently, polyclonal antibodies against mouse derived UL23 were employed to reveal that wild type UL23 was mainly located in the nucleus during PRV infection. Co-expression of UL23 with SUMO deconjugating enzymes showed that SENP1/2 inhibited the nuclear import of UL23. Whereas SUMO modification significantly impacted the localization of UL23, it did not detectably affect its stability.