mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
Qinghua Luo,
Li Zhang,
Feng Wei,
Qiang Fang,
Fei Bao,
Shijiang Mi,
Nan Li,
Chengming Wang,
Yan Liu,
Changchun Tu
Affiliations
Qinghua Luo
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
Li Zhang
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China
Feng Wei
Department of Hepatobiliary & Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Qiang Fang
Department of Hepatobiliary & Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Fei Bao
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China
Shijiang Mi
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China
Nan Li
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China
Chengming Wang
Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
Yan Liu
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China; Corresponding author
Changchun Tu
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Corresponding author
Summary: Classical swine fever virus (CSFV) can utilize diverse host signaling pathways for its replication; however, the cross talk between mammalian target of rapamycin (mTOR) and CSFV remains unknown. Here, we describe the potential role of mTOR complex 1 (mTORC1) in promoting CSFV replication via virus-induced hypophosphorylation of the Akt/mTORC1/S6 pathway, especially at an early stage of viral infection. Conversely, activation of mTORC1 inhibited the replication of CSFV. Furthermore, we revealed the underlying mechanisms of mTORC1 pathway in mediating CSFV replication; in addition, our data also showed that CSFV-induced transient inhibition of mTORC1 elicited a negative feedback activation of PI3K/Akt/mTORC1pathway, likely contributing to maintain the dynamic balance between viral replication and host cell survival. This study has provided strong evidence showing how CSFV utilizes mTORC1 pathway for viral replication at an early stage in the viral replicative cycle and how the mTORC1 rescues itself by eliciting a feedback loop to limit viral replication and maintain cell survival. : Pathophysiology; Molecular Biology; Virology Subject Areas: Pathophysiology, Molecular Biology, Virology
