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Article

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

1
Department of Pathology, Riga Stradins University, LV-1007 Riga, Latvia
2
Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
3
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
4
N.F. Gamaleya Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
5
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
6
RE Kavetsky Institite of Experimental Pathology, Oncology and Radiobiology, The National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine
7
MP Chumakov Center for Research and Development of Immune and Biological Preparations of RAS, 108819 Moscow, Russia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(3), 208; https://doi.org/10.3390/cells8030208
Received: 22 November 2018 / Revised: 6 February 2019 / Accepted: 20 February 2019 / Published: 28 February 2019
(This article belongs to the Special Issue Hepatitis C Virus and Host Interactions)
HCV 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. View Full-Text
Keywords: Hepatitis C virus; nucleocapsid (core); DNA-immunization; oxidative stress; cellular immune response; predictive marker Hepatitis C virus; nucleocapsid (core); DNA-immunization; oxidative stress; cellular immune response; predictive marker
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MDPI and ACS Style

Jansons, 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. The Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Response. Cells 2019, 8, 208. https://doi.org/10.3390/cells8030208

AMA Style

Jansons J, Sominskaya I, Petrakova N, Starodubova ES, Smirnova OA, Alekseeva E, Bruvere R, Eliseeva O, Skrastina D, Kashuba E, Mihailova M, Kochetkov SN, Ivanov AV, Isaguliants MG. The Immunogenicity in Mice of HCV Core Delivered as DNA Is Modulated by Its Capacity to Induce Oxidative Stress and Oxidative Stress Response. Cells. 2019; 8(3):208. https://doi.org/10.3390/cells8030208

Chicago/Turabian Style

Jansons, Juris; Sominskaya, Irina; Petrakova, Natalia; Starodubova, Elizaveta S.; Smirnova, Olga A.; Alekseeva, Ekaterina; Bruvere, Ruta; Eliseeva, Olesja; Skrastina, Dace; Kashuba, Elena; Mihailova, Marija; Kochetkov, Sergey N.; Ivanov, Alexander V.; Isaguliants, Maria 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 8, no. 3: 208. https://doi.org/10.3390/cells8030208

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