HCV core protein uses multiple mechanisms to induce oxidative stress in human hepatoma huh7 cells

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dc.contributor.authorIvanov, Alexander V.
dc.contributor.authorSmirnova, Olga A.
dc.contributor.authorPetrushanko, Irina Y.
dc.contributor.authorIvanova, Olga N.
dc.contributor.authorKarpenko, Inna L.
dc.contributor.authorAlekseeva, Ekaterina
dc.contributor.authorSominskaya, Irina
dc.contributor.authorMakarov, Alexander A.
dc.contributor.authorBartosch, Birke
dc.contributor.authorKochetkov, Sergey N.
dc.contributor.authorIsaguliants, Maria G.
dc.contributor.institutionInstitute of Microbiology and Virology
dc.date.accessioned2021-07-02T09:50:01Z
dc.date.available2021-07-02T09:50:01Z
dc.date.issued2015-05-29
dc.descriptionPublisher Copyright: © 2015 by the authors; licensee MDPI, Basel, Switzerland.
dc.description.abstractHepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein.en
dc.description.statusPeer reviewed
dc.format.extent26
dc.format.extent2008942
dc.identifier.citationIvanov, A V, Smirnova, O A, Petrushanko, I Y, Ivanova, O N, Karpenko, I L, Alekseeva, E, Sominskaya, I, Makarov, A A, Bartosch, B, Kochetkov, S N & Isaguliants, M G 2015, 'HCV core protein uses multiple mechanisms to induce oxidative stress in human hepatoma huh7 cells', Viruses, vol. 7, no. 6, pp. 2745-2770. https://doi.org/10.3390/v7062745
dc.identifier.doi10.3390/v7062745
dc.identifier.issn1999-4915
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/5818
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84930937748&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofViruses
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCytochrome P450
dc.subjectER oxidoreductin
dc.subjectHepatitis C virus
dc.subjectNADPH oxidase
dc.subjectOxidative stress
dc.subjectReactive oxygen species
dc.subjectTransforming growth factor
dc.subject3.1 Basic medicine
dc.subject3.3 Health sciences
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectInfectious Diseases
dc.subjectVirology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleHCV core protein uses multiple mechanisms to induce oxidative stress in human hepatoma huh7 cellsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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