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Article

Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway

1
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece
2
GP Livanos and M Simou Laboratories, 1st Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, 10676 Athens, Greece
3
Section of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece
*
Author to whom correspondence should be addressed.
Equal contribution.
Deceased.
Academic Editors: Ioannis Karakasiliotis, Apostolos Beloukas and Serafeim Chaintoutis
Viruses 2021, 13(11), 2139; https://doi.org/10.3390/v13112139
Received: 29 September 2021 / Revised: 15 October 2021 / Accepted: 19 October 2021 / Published: 23 October 2021
(This article belongs to the Special Issue State-of-the-Art Virus Research in Greece)
A bidirectional negative relationship between Hepatitis C virus (HCV) replication and gene expression of the catecholamine biosynthetic enzyme L-Dopa decarboxylase (DDC) was previously shown in the liver and attributed at least to an association of DDC with phosphatidylinositol 3-kinase (PI3K). Here, we report that the biosynthesis and uptake of catecholamines restrict HCV replication in hepatocytes, while HCV has developed ways to reduce catecholamine production. By employing gene silencing, chemical inhibition or induction of the catecholamine biosynthetic and metabolic enzymes and transporters, and by applying the substrates or the products of the respective enzymes, we unravel the role of the different steps of the pathway in viral infection. We also provide evidence that the effect of catecholamines on HCV is strongly related with oxidative stress that is generated by their autoxidation in the cytosol, while antioxidants or treatments that lower cytosolic catecholamine levels positively affect the virus. To counteract the effect of catecholamines, HCV, apart from the already reported effects on DDC, causes the down-regulation of tyrosine hydroxylase that encodes the rate-limiting enzyme of catecholamine biosynthesis and suppresses dopamine beta-hydroxylase mRNA and protein amounts, while increasing the catecholamine degradation enzyme monoamine oxidase. Moreover, the NS4B viral protein is implicated in the effect of HCV on the ratio of the ~50 kDa DDC monomer and a ~120 kDa DDC complex, while the NS5A protein has a negative effect on total DDC protein levels. View Full-Text
Keywords: Hepatitis C virus; viral replication; catecholamine biosynthetic/metabolic pathway; L-Dopa decarboxylase; tyrosine hydroxylase; dopamine beta-hydroxylase; monoamine oxidase Hepatitis C virus; viral replication; catecholamine biosynthetic/metabolic pathway; L-Dopa decarboxylase; tyrosine hydroxylase; dopamine beta-hydroxylase; monoamine oxidase
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MDPI and ACS Style

Mpekoulis, G.; Tsopela, V.; Panos, G.; Siozos, V.; Kalliampakou, K.I.; Frakolaki, E.; Sideris, C.D.; Vassiliou, A.G.; Sideris, D.C.; Vassilacopoulou, D.; Vassilaki, N. Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway. Viruses 2021, 13, 2139. https://doi.org/10.3390/v13112139

AMA Style

Mpekoulis G, Tsopela V, Panos G, Siozos V, Kalliampakou KI, Frakolaki E, Sideris CD, Vassiliou AG, Sideris DC, Vassilacopoulou D, Vassilaki N. Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway. Viruses. 2021; 13(11):2139. https://doi.org/10.3390/v13112139

Chicago/Turabian Style

Mpekoulis, George, Vassilina Tsopela, Georgios Panos, Vasileiοs Siozos, Katerina I. Kalliampakou, Efseveia Frakolaki, Constantinos D. Sideris, Alice G. Vassiliou, Diamantis C. Sideris, Dido Vassilacopoulou, and Niki Vassilaki. 2021. "Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway" Viruses 13, no. 11: 2139. https://doi.org/10.3390/v13112139

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