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

作者：Luo, Qinghua; Zhang, Li; Wei, Feng; Fang, Qiang; Bao, Fei; Mi, Shijiang; Li, Nan; Wang, Chengming; Liu, Yan^*; Tu, Changchun^*

来源：iScience, 2018, 3: 87-+.

DOI：10.1016/j.isci.2018.04.010

• HEPATITIS-C-VIRUS
• NS5A PROTEIN
• E2-INTERACTING PROTEIN
• MAMMALIAN TARGET
• ENTRY SITE
• INHIBITION
• GROWTH
• RNA
• AKT
• ACTIVATION

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/mTORC1 pathway, 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.

• 出版日期2018-5-25
• 单位吉林大学; 扬州大学; 中国人民解放军军事医学科学院