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13:04
A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
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Pyruvate dehydrogenase kinase regulates hepatitis C virus replication
Gwon-Soo Jung1,2, Jae-Han Jeon1,2, Yeon-Kyung Choi1,2
1Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Scientific Reports
|July 30, 2016
Summary
Hepatitis C virus (HCV) infection alters host cell metabolism, increasing glycolysis and nucleotide synthesis. Inhibiting pyruvate dehydrogenase kinase (PDK) suppressed viral replication, suggesting PDK as a therapeutic target.
Area of Science:
- Virology
- Cellular Metabolism
- Biochemistry
Background:
- Hepatitis C virus (HCV) replication depends on host cell macromolecules.
- HCV infection necessitates host cellular metabolic reprogramming towards aerobic glycolysis.
Purpose of the Study:
- To investigate the role of pyruvate dehydrogenase kinase (PDK) in regulating HCV replication.
- To determine if targeting PDK can inhibit HCV.
Main Methods:
- Compared protein and mRNA expression of metabolic regulators (c-Myc, HIF-1α, PDKs, glycolytic enzymes) in HCV-infected vs. uninfected cells.
- Utilized c-Myc inhibitor (JQ1) and PDK inhibitor (dichloroacetate, DCA).
- Assessed viral replication and enzyme expression following inhibitor treatment, alone and with IFN-α or ribavirin.
Main Results:
- HCV infection significantly upregulated c-Myc, HIF-1α, glycolytic, and serine biosynthetic enzymes.
- JQ1 and DCA decreased these enzymes in infected cells, suppressing viral replication.
- DCA enhanced the antiviral effects of IFN-α and ribavirin.
Conclusions:
- HCV reprograms host metabolism to favor glycolysis and serine biosynthesis, partly via increased PDK activity.
- Increased PDK activity supplies nucleotide precursors essential for viral replication.
- Blocking PDK activity shows therapeutic potential against HCV.
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