{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:29:45Z","timestamp":1772252985346,"version":"3.50.1"},"reference-count":97,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvijas Zin\u0101tnes Padome","doi-asserted-by":"publisher","award":["LZP-2018\/2-0308"],"award-info":[{"award-number":["LZP-2018\/2-0308"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005375","name":"Latvijas Zin\u0101tnes Padome","doi-asserted-by":"publisher","award":["LZP-2020\/2-0376"],"award-info":[{"award-number":["LZP-2020\/2-0376"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","award":["FoBe 2018-02329"],"award-info":[{"award-number":["FoBe 2018-02329"]}],"id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor-associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB\/c mice, inducing IFN-\u03b3\/IL-2\/TNF-\u03b1 response of CD4+ and CD8+ T cells. Additionally, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescence signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-\u03b2 promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-\u03b2 driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length\/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.<\/jats:p>","DOI":"10.3390\/microorganisms9051073","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T12:19:57Z","timestamp":1621253997000},"page":"1073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-4392","authenticated-orcid":false,"given":"Juris","family":"Jansons","sequence":"first","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, LV-1007 Riga, Latvia"},{"name":"Latvian Biomedical Research and Study Centre,  LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dace","family":"Skrastina","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre,  LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa","family":"Kurlanda","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, LV-1007 Riga, Latvia"},{"name":"Latvian Biomedical Research and Study Centre,  LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-9646","authenticated-orcid":false,"given":"Stefan","family":"Petkov","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8168-5969","authenticated-orcid":false,"given":"Darya","family":"Avdoshina","sequence":"additional","affiliation":[{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and Biological Products of Russian Academy of Sciences, 108819 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Kuzmenko","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Krotova","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Trofimova","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, LV-1007 Riga, Latvia"},{"name":"Latvian Biomedical Research and Study Centre,  LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4551-7535","authenticated-orcid":false,"given":"Ilya","family":"Gordeychuk","sequence":"additional","affiliation":[{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and Biological Products of Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"Institute of Translational Medicine and Biotechnology, Sechenov Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1932-369X","authenticated-orcid":false,"given":"Irina","family":"Sominskaya","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre,  LV-1067 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-2254","authenticated-orcid":false,"given":"Maria","family":"Isaguliants","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, Riga Stradins University, LV-1007 Riga, Latvia"},{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden"},{"name":"Chumakov Federal Scientific Center for Research and Development of Immune-and Biological Products of Russian Academy of Sciences, 108819 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.coviro.2017.03.014","article-title":"Designing an HCV vaccine: A unique convergence of prevention and therapy?","volume":"23","author":"Walker","year":"2017","journal-title":"Curr. 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