title: Hepatitis C virus alters metabolism of biogenic polyamines by affecting expression of key enzymes of their metabolism.
abstract: Chronic infection with hepatitis C virus (HCV) induces liver fibrosis and cancer. In particular metabolic alterations and associated oxidative stress induced by the virus play a key role in disease progression. Albeit the pivotal role of biogenic polyamines spermine and spermidine in the regulation of liver metabolism and function and cellular control of redox homeostasis, their role in the viral life cycle has not been studied so far. Here we show that in cell lines expressing two viral proteins, capsid and the non-structural protein 5A, expression of the two key enzymes of polyamine biosynthesis and degradation, respectively, ornithine decarboxylase (ODC) and spermidine/spermine-N1-acetyl transferase (SSAT), increases transiently. In addition, both HCV core and NS5A induce sustained expression of spermine oxidase (SMO), an enzyme that catalyzes conversion of spermine into spermidine. Human hepatoma Huh7 cells harboring a full-length HCV replicon exhibited suppressed ODC and SSAT levels and elevated levels of SMO leading to decreased intracellular concentrations of spermine and spermidine. Thus, role of HCV-driven alterations of polyamine metabolism in virus replication and development of HCV-associated liver pathologies should be explored in future.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Smirnova
authors.affiliation: School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tuomo A
authors.initials: TA
authors.lastname: Keinanen
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Ivanova
authors.affiliation: School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mervi T
authors.initials: MT
authors.lastname: Hyvonen
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Khomutov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
authors.affiliation: Inserm U1052, Cancer Research Center of Lyon, University of Lyon, Lyon, France; DevWeCan Laboratories of Excellence Network (Labex), France.
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. Electronic address: aivanov@yandex.ru.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ivanov
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D015317:Biogenic Polyamines / Q000378:metabolism*; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D014758:Viral Core Proteins / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000502:physiology; D014779:Virus Replication / Q000502:physiology; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000123:Acetyltransferases; D015317:Biogenic Polyamines; D009955:Ornithine Decarboxylase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D013095:Spermidine; D013096:Spermine; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Hepatitis C virus; Metabolism; Polyamines; Spermidine; Spermine