The Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Response

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dc.contributor.authorJansons, Juris
dc.contributor.authorSominskaya, Irina
dc.contributor.authorPetrakova, Natalia
dc.contributor.authorStarodubova, Elizaveta S.
dc.contributor.authorSmirnova, Olga A.
dc.contributor.authorAlekseeva, Ekaterina
dc.contributor.authorBruvere, Ruta
dc.contributor.authorEliseeva, Olesja
dc.contributor.authorSkrastina, Dace
dc.contributor.authorKashuba, Elena
dc.contributor.authorMihailova, Marija
dc.contributor.authorKochetkov, Sergey N.
dc.contributor.authorIvanov, Alexander V.
dc.contributor.authorIsaguliants, Maria G.
dc.contributor.institutionDepartment of Pathology
dc.date.accessioned2023-12-18T13:50:01Z
dc.date.available2023-12-18T13:50:01Z
dc.date.issued2019-02-28
dc.description.abstractHCV core is an attractive HCV vaccine target, however, clinical or preclinical trials of core-based vaccines showed little success. We aimed to delineate what restricts its immunogenicity and improve immunogenic performance in mice. We designed plasmids encoding full-length HCV 1b core and its variants truncated after amino acids (aa) 60, 98, 152, 173, or up to aa 36 using virus-derived or synthetic polynucleotides (core191/60/98/152/173/36_191v or core152s DNA, respectively). We assessed their level of expression, route of degradation, ability to trigger the production of reactive oxygen species/ROS, and to activate the components of the Nrf2/ARE antioxidant defense pathway heme oxygenase 1/HO-1 and NAD(P)H: quinone oxidoreductase/Nqo-1. All core variants with the intact N-terminus induced production of ROS, and up-regulated expression of HO-1 and Nqo-1. The capacity of core variants to induce ROS and up-regulate HO-1 and Nqo-1 expression predetermined their immunogenicity in DNA-immunized BALB/c and C57BL/6 mice. The most immunogenic was core 152s, expressed at a modest level and inducing moderate oxidative stress and oxidative stress response. Thus, immunogenicity of HCV core is shaped by its ability to induce ROS and oxidative stress response. These considerations are important in understanding the mechanisms of viral suppression of cellular immune response and in HCV vaccine design.en
dc.description.statusPeer reviewed
dc.format.extent3767039
dc.identifier.citationJansons, J, Sominskaya, I, Petrakova, N, Starodubova, E S, Smirnova, O A, Alekseeva, E, Bruvere, R, Eliseeva, O, Skrastina, D, Kashuba, E, Mihailova, M, Kochetkov, S N, Ivanov, A V & Isaguliants, M G 2019, 'The Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Response', Cells, vol. 8, no. 3, 208. https://doi.org/10.3390/cells8030208
dc.identifier.doi10.3390/cells8030208
dc.identifier.issn2073-4409
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/15060
dc.language.isoeng
dc.relation.ispartofCells
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHepatitis C virus
dc.subjectnucleocapsid (core)
dc.subjectDNA-immunization
dc.subjectoxidative stress
dc.subjectcellular immune response
dc.subjectpredictive marker
dc.subject3.1 Basic medicine
dc.subject3.2 Clinical medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectSDG 3 - Good Health and Well-being
dc.titleThe Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Responseen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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