MTORC1 Promotes SARS-CoV-2 Replication and Attenuates Type I Interferon Responses in the Alveolar Epithelium: A Computational and Experimental Study.

ABSTRACT: The mechanistic target of rapamycin complex 1 (mTORC1) has been implicated in coronavirus pathogenesis, yet its precise role in shaping antiviral defenses in pneumocytes remains unresolved. This study combines ex vivo human lung tissue assays with a literature-curated, logic-based (Boolean) signaling model to study how mTORC1 influences SARS-CoV-2 replication and type-I interferon (IFN) responses. Our in-vitro data showed that pharmacologic inhibition of mTORC1 with sirolimus was associated with reduced viral replication and increased IFN- β expression across donor samples. To interpret these data, we constructed a network integrating inflammation, stress, apoptosis, and RIG-I-IFN signaling, and evaluated four mechanistic hypotheses for explaining our experiments in which mTORC1 either pro

SUBMITTER: Kutuva AR 

PROVIDER: S-EPMC13538202 | biostudies-literature | 2026 Sep

REPOSITORIES: biostudies-literature