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Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism
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SYSNO ASEP 0549782 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism Author(s) Pilná, H. (CZ)
Hájková, V. (CZ)
Knitlová, Jarmila (FGU-C) RID, ORCID
Lišková, Jana (FGU-C) RID, ORCID
Elsterová, Jana (BC-A) ORCID
Melková, Z. (CZ)Article number 1986 Source Title Viruses. - : MDPI
Roč. 13, č. 10 (2021)Number of pages 20 s. Language eng - English Country CH - Switzerland Keywords IRF-3 ; vaccinia virus ; smallpox ; atopic dermatitis ; eczema vaccinatum ; immunization ; interferon beta ; interleukin-1 beta ; cytokines ; Nc/Nga mice Subject RIV EI - Biotechnology ; Bionics OECD category Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction) Subject RIV - cooperation Biology Centre (since 2006) - Microbiology, Virology R&D Projects LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) TN01000013 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) Method of publishing Open access Institutional support FGU-C - RVO:67985823 ; BC-A - RVO:60077344 UT WOS 000713116900001 EID SCOPUS 85116464105 DOI 10.3390/v13101986 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://www.mdpi.com/1999-4915/13/10/1986
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