PMID- 22915817 OWN - NLM STAT- MEDLINE DCOM- 20130111 LR - 20240316 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 86 IP - 22 DP - 2012 Nov TI - Porcine circovirus type 2 induces autophagy via the AMPK/ERK/TSC2/mTOR signaling pathway in PK-15 cells. PG - 12003-12 LID - 10.1128/JVI.01434-12 [doi] AB - 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. FAU - Zhu, Binglin AU - Zhu B AD - Zhejiang University Institute of Preventive Veterinary Medicine, Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, Hangzhou, People's Republic of China. FAU - Zhou, Yingshan AU - Zhou Y FAU - Xu, Fei AU - Xu F FAU - Shuai, Jiangbing AU - Shuai J FAU - Li, Xiaoliang AU - Li X FAU - Fang, Weihuan AU - Fang W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120822 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (RNA, Small Interfering) RN - 0 (Tuberous Sclerosis Complex 2 Protein) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Animals MH - *Autophagy MH - Cell Line MH - Circoviridae Infections/*metabolism MH - Circovirus/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Gene Expression Regulation, Viral MH - Models, Biological MH - Phosphorylation MH - RNA, Small Interfering/metabolism MH - Signal Transduction MH - Swine MH - TOR Serine-Threonine Kinases/*metabolism MH - Tuberous Sclerosis Complex 2 Protein MH - Tumor Suppressor Proteins/*metabolism PMC - PMC3486458 EDAT- 2012/08/24 06:00 MHDA- 2013/01/12 06:00 PMCR- 2013/05/01 CRDT- 2012/08/24 06:00 PHST- 2012/08/24 06:00 [entrez] PHST- 2012/08/24 06:00 [pubmed] PHST- 2013/01/12 06:00 [medline] PHST- 2013/05/01 00:00 [pmc-release] AID - JVI.01434-12 [pii] AID - 01434-12 [pii] AID - 10.1128/JVI.01434-12 [doi] PST - ppublish SO - J Virol. 2012 Nov;86(22):12003-12. doi: 10.1128/JVI.01434-12. Epub 2012 Aug 22.