mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation

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 vi...

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Main Authors: Qinghua Luo, Li Zhang, Feng Wei, Qiang Fang, Fei Bao, Shijiang Mi, Nan Li, Chengming Wang, Yan Liu, Changchun Tu
Format: Article
Language:English
Published: Elsevier 2018-05-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004218300427
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author Qinghua Luo
Li Zhang
Feng Wei
Qiang Fang
Fei Bao
Shijiang Mi
Nan Li
Chengming Wang
Yan Liu
Changchun Tu
author_facet Qinghua Luo
Li Zhang
Feng Wei
Qiang Fang
Fei Bao
Shijiang Mi
Nan Li
Chengming Wang
Yan Liu
Changchun Tu
author_sort Qinghua Luo
collection DOAJ
description 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
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spelling doaj.art-890a43dfbba54ab8b1d984b6eeba329e2022-12-21T21:51:49ZengElsevieriScience2589-00422018-05-01387101mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent TranslationQinghua Luo0Li Zhang1Feng Wei2Qiang Fang3Fei Bao4Shijiang Mi5Nan Li6Chengming Wang7Yan Liu8Changchun Tu9Key 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. ChinaKey Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. ChinaDepartment of Hepatobiliary & Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. ChinaDepartment of Hepatobiliary & Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. ChinaKey Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. ChinaKey Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. ChinaKey Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. ChinaJiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. ChinaKey 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 authorKey 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 authorSummary: 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, Virologyhttp://www.sciencedirect.com/science/article/pii/S2589004218300427
spellingShingle Qinghua Luo
Li Zhang
Feng Wei
Qiang Fang
Fei Bao
Shijiang Mi
Nan Li
Chengming Wang
Yan Liu
Changchun Tu
mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
iScience
title mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
title_full mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
title_fullStr mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
title_full_unstemmed mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
title_short mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation
title_sort mtorc1 negatively regulates the replication of classical swine fever virus through autophagy and ires dependent translation
url http://www.sciencedirect.com/science/article/pii/S2589004218300427
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