Porcine circovirus type 2 induces autophagy via the AMPK/ERK/TSC2/mTOR signaling pathway in PK-15 cells.
Porcine circovirus type 2 (PCV2) uses autophagy machinery to enhance its replication in PK-15 cells. However, the underlying mechanisms are unknown. By the use of specific inhibitors, RNA interference, and coimmunoprecipitation, we show that PCV2 induces autophagy in PK-15 cells through a pathway involving the kinases AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2), the tumor suppressor protein TSC2, and the mammalian target of rapamycin (mTOR). AMPK and ERK1/2 positively regulate autophagy through negative control of the mTOR pathway by phosphorylating TSC2 in PCV2-infected PK-15 cells. Thus, PCV2 might induce autophagy via the AMPK/ERK/TSC2/mTOR signaling pathway in the host cells, representing a pivotal mechanism for PCV2 pathogenesis.
Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, Hangzhou, People's Republic of China.
Binglin
B
Zhu
Yingshan
Y
Zhou
Fei
F
Xu
Jiangbing
J
Shuai
Xiaoliang
X
Li
Weihuan
W
Fang
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D018173:Circoviridae Infections / Q000378:metabolism*; D017925:Circovirus / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D008954:Models, Biological; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D034741:RNA, Small Interfering; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases