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Published on: May 15, 2014
AMP-activated protein kinase (AMPK) suppresses Ibaraki virus propagation
Kiichi Ohkubo1, Shusaku Shibutani1, Hiroyuki Iwata1
1Laboratory of Veterinary Hygiene, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8515, Japan.
Abstract:
The Ibaraki virus (IBAV) causes Ibaraki disease in cattle. Our previous studies have shown that IBAV uses macropinocytosis to enter the host cell and exit from the endosome to the cytosol in response to endosomal acidification. To further explore the mechanism of IBAV infection and replication, we examined the effect of inhibitors of mitochondrial oxidative phosphorylation, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and antimycin A, on IBAV propagation. These inhibitors significantly suppressed IBAV propagation, with reduced cellular ATP levels resulting from suppression of ATP synthesis. Furthermore, we identified AMP-activated protein kinase (AMPK), which is activated by CCCP or antimycin A, as a key signaling molecule in IBAV suppression. We also observed that IBAV infection induces ATP depletion and increases AMPK activity. Our findings suggest that AMPK is a potential target in Ibaraki disease.
Insights
Ibaraki virus (IBAV) propagation is suppressed by inhibiting mitochondrial ATP synthesis. AMP-activated protein kinase (AMPK) activation by these inhibitors, and during IBAV infection, suggests it is a key factor in controlling Ibaraki disease.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Ibaraki virus (IBAV) causes significant disease in cattle.
- IBAV infection involves macropinocytosis and endosomal escape, triggered by acidification.
- Understanding IBAV replication mechanisms is crucial for disease control.
Purpose of the Study:
- To investigate the role of mitochondrial oxidative phosphorylation in IBAV replication.
- To identify host factors involved in IBAV propagation and suppression.
- To explore potential therapeutic targets for Ibaraki disease.
Main Methods:
- Treatment of infected cells with mitochondrial inhibitors (CCCP, antimycin A).
- Measurement of cellular ATP levels and ATP synthesis.
- Analysis of AMP-activated protein kinase (AMPK) activation.
- Monitoring of IBAV propagation in treated and infected cells.
Main Results:
- Inhibitors of mitochondrial oxidative phosphorylation significantly suppressed IBAV propagation.
- Suppression of propagation correlated with reduced cellular ATP levels.
- CCCP and antimycin A activated AMPK, which was also activated during IBAV infection.
- IBAV infection itself led to ATP depletion and increased AMPK activity.
Conclusions:
- Mitochondrial ATP synthesis is essential for efficient Ibaraki virus replication.
- AMP-activated protein kinase (AMPK) plays a critical role in suppressing IBAV propagation.
- AMPK activation represents a potential therapeutic strategy for managing Ibaraki disease in cattle.
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