{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:24:43Z","timestamp":1760235883627,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education of the Czech Republic, National Sustainability Program II","award":["Project BIOCEV-FAR No. LQ1604"],"award-info":[{"award-number":["Project BIOCEV-FAR No. LQ1604"]}]},{"DOI":"10.13039\/100007543","name":"Grantov\u00e1 Agentura, Univerzita Karlova","doi-asserted-by":"publisher","award":["Project No. 100307"],"award-info":[{"award-number":["Project No. 100307"]}],"id":[{"id":"10.13039\/100007543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Project No. Progres Q26 \u2013 206026-3"],"award-info":[{"award-number":["Project No. Progres Q26 \u2013 206026-3"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encodes various factors interfering with host immune responses at multiple levels. In atopic skin, the production of type I interferon is compromised, while VACV specifically inhibits the phosphorylation of the Interferon Regulatory Factor 3 (IRF-3) and expression of interferons. To overcome this block, we generated a recombinant VACV-expressing murine IRF-3 (WR-IRF3) and characterized its effects on virus growth, cytokine expression and apoptosis in tissue cultures and in spontaneously atopic Nc\/Nga and control Balb\/c mice. Further, we explored the induction of protective immune responses against a lethal dose of wild-type WR, the surrogate of smallpox. We demonstrate that the overexpression of IRF-3 by WR-IRF3 increases the expression of type I interferon, modulates the expression of several cytokines and induces superior protective immune responses against a lethal poxvirus challenge in both Nc\/Nga and Balb\/c mice. Additionally, the results may be informative for design of other virus-based vaccines or for therapy of different viral infections.<\/jats:p>","DOI":"10.3390\/v13101986","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"1986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism"],"prefix":"10.3390","volume":"13","author":[{"given":"Hana","family":"Pilna","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, First Faculty of Medicine, Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic"},{"name":"BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Pr\u016fmyslov\u00e1 595, 252 50 Vestec, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Hajkova","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, First Faculty of Medicine, Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic"},{"name":"BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Pr\u016fmyslov\u00e1 595, 252 50 Vestec, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-4497","authenticated-orcid":false,"given":"Jarmila","family":"Knitlova","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, First Faculty of Medicine, Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Liskova","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, First Faculty of Medicine, Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-3092","authenticated-orcid":false,"given":"Jana","family":"Elsterova","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, First Faculty of Medicine, Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9709-2110","authenticated-orcid":false,"given":"Zora","family":"Melkova","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, First Faculty of Medicine, Charles University, Studnickova 7, 128 00 Prague 2, Czech Republic"},{"name":"BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Pr\u016fmyslov\u00e1 595, 252 50 Vestec, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/rmv.571","article-title":"New generation smallpox vaccines: A review of preclinical and clinical data","volume":"18","author":"Artenstein","year":"2008","journal-title":"Rev. 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