EBNA1 SUMOylation by PIAS1 Suppresses EBV Lytic Replication and Enhances Episome Maintenance.

ABSTRACT: Epstein-Barr virus nuclear antigen 1 (EBNA1) is essential for the replication and stable maintenance of the viral episome in infected cells. Here, we identify the SUMO E3 ligase PIAS1 as a key regulator of EBNA1 through site-specific SUMOylation. Our Chromatin-Immunoprecipitation Sequencing (ChIP-seq) analysis revealed that PIAS1 is enriched at the viral origin of plasmid replication ( oriP ), where it physically associates with EBNA1 and catalyzes its SUMOylation. Using mutational analysis, we identified three lysine residues on EBNA1 (K17, K75, and K241) as major SUMOylation sites. Disruption of these sites compromises EBNA1's ability to restrict EBV lytic replication. In addition, both PIAS1 depletion and the disruption of EBNA1 SUMOylation lead to reduced retention of EBNA1-

SUBMITTER: Sugiokto FG 

PROVIDER: S-EPMC12424706 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature