SARS-CoV-2 Nsp15 endoribonuclease subverts host defenses to enhance viral fitness in lung cells.

ABSTRACT: Coronaviruses encode nonstructural protein 15 (Nsp15), a conserved endoribonuclease (EndoU) known to suppress host antiviral responses. It is imperative to understand the role of Nsp15/EndoU during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in its primary target respiratory epithelial cells. Using a recombinant wild-type SARS-CoV-2 (rWT) and a mutant with catalytically inactive EndoU (rH234A), we show that the EndoU activity is dispensable for viral replication in Vero cells but critically facilitates immune suppression and infection in physiologically relevant human lung cells, including human lung-derived epithelial cell lines, primary bronchial air-liquid interface cultures, and alveolar type 2 organoids derived from induced pluripotent stem cells. Compared t

SUBMITTER: Chi X 

PROVIDER: S-EPMC12456009 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature