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.

Virology
|December 16, 2023
PubMed

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.

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...