PMID- 27213427
OWN - NLM
STAT- MEDLINE
DCOM- 20170920
LR  - 20181113
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 8
IP  - 5
DP  - 2016 May 20
TI  - Porcine Circovirus Type 2 Activates CaMMKbeta to Initiate Autophagy in PK-15 Cells 
      by Increasing Cytosolic Calcium.
LID - 10.3390/v8050135 [doi]
LID - 135
AB  - Porcine circovirus type 2 (PCV2) induces autophagy via the 5' adenosine 
      monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated 
      kinase (ERK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin 
      (mTOR) pathway in pig kidney PK-15 cells. However, the underlying mechanisms of 
      AMPK activation in autophagy induction remain unknown. With specific inhibitors 
      and RNA interference (RNAi), we show that PCV2 infection upregulated 
      calcium/calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) by increasing 
      cytosolic Ca(2+) via inositol 1,4,5-trisphosphate receptor (IP3R). Elevation of 
      cytosolic calcium ion (Ca(2+)) did not seem to involve inositol 
      1,4,5-trisphosphate (IP3) release from phosphatidylinositol 4,5-bisphosphate 
      (PIP2) by phosphoinositide phospholipase C-gamma (PLC-gamma). CaMKKbeta then activated 
      both AMPK and calcium/calmodulin-dependent protein kinase I (CaMKI). PCV2 
      employed CaMKI and Trp-Asp (WD) repeat domain phosphoinositide-interacting 
      protein 1 (WIPI1) as another pathway additional to AMPK signaling in autophagy 
      initiation. Our findings could help better understanding of the signaling 
      pathways of autophagy induction as part of PCV2 pathogenesis. Further research is 
      warranted to study if PCV2 interacts directly with IP3R or indirectly with the 
      molecules that antagonize IP3R activity responsible for increased cytosolic 
      Ca(2+) both in PK-15 cells and PCV2-targeted primary cells from pigs.
FAU - Gu, Yuanxing
AU  - Gu Y
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      guzi.123@163.com.
FAU - Qi, Baozhu
AU  - Qi B
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      qibaozhu@yeah.net.
FAU - Zhou, Yingshan
AU  - Zhou Y
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      yszhou@zju.edu.cn.
FAU - Jiang, Xiaowu
AU  - Jiang X
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      cqrcxwj@163.com.
FAU - Zhang, Xian
AU  - Zhang X
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      zhangxian073@163.com.
FAU - Li, Xiaoliang
AU  - Li X
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      xlli@zju.edu.cn.
FAU - Fang, Weihuan
AU  - Fang W
AD  - Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Institute 
      of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China. 
      whfang@zju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160520
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 1)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - *Autophagy
MH  - Calcium/*metabolism
MH  - *Calcium Signaling
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 1/metabolism
MH  - Cell Line
MH  - Circovirus/*pathogenicity
MH  - Epithelial Cells/physiology/virology
MH  - *Host-Pathogen Interactions
MH  - Inositol 1,4,5-Trisphosphate Receptors/metabolism
MH  - Swine
PMC - PMC4885090
OTO - NOTNLM
OT  - Ca2+ signaling
OT  - autophagy
OT  - pathogenesis
OT  - porcine circovirus 2
EDAT- 2016/05/24 06:00
MHDA- 2017/09/21 06:00
PMCR- 2016/05/01
CRDT- 2016/05/24 06:00
PHST- 2016/03/12 00:00 [received]
PHST- 2016/05/11 00:00 [revised]
PHST- 2016/05/12 00:00 [accepted]
PHST- 2016/05/24 06:00 [entrez]
PHST- 2016/05/24 06:00 [pubmed]
PHST- 2017/09/21 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - v8050135 [pii]
AID - viruses-08-00135 [pii]
AID - 10.3390/v8050135 [doi]
PST - epublish
SO  - Viruses. 2016 May 20;8(5):135. doi: 10.3390/v8050135.