SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness.

ABSTRACT: Coronaviruses (CoVs) maintain large RNA genomes that frequently undergo mutations and recombination, contributing to their evolution and emergence. In this study, we find that SARS-CoV-2 has greater RNA recombination frequency than other human CoVs. In addition, CoV RNA recombination primarily occurs at uridine (U)-enriched RNA sequences. Therefore, we next evaluate the role of SARS-CoV-2 NSP15, a viral endonuclease that targets uridines (EndoU), in RNA recombination and virus infection. Using a catalytically inactivated EndoU mutant (NSP15^H234A), we observe attenuated viral replication in vitro and in vivo. However, the loss of EndoU activity also dysregulates inflammation resulting in similar disease in vivo despite reduced viral loads. Next-generation sequencing (NGS) demonst

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12783608 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature