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.

• Klíčová slova
• IRF-3, Nc/Nga mice, atopic dermatitis, cytokines, eczema vaccinatum, immunization, interferon beta, interleukin-1 beta, smallpox, vaccinia virus,
• MeSH
• exprese genu genetika   MeSH
• imunita imunologie   MeSH
• infekce vyvolané poxviry imunologie   prevence a kontrola   MeSH
• interferon typ I metabolismus   MeSH
• interferonový regulační faktor 3 genetika   imunologie   MeSH
• interleukin-1beta imunologie   MeSH
• kůže imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• Poxviridae patogenita   MeSH
• regulace exprese virových genů genetika   MeSH
• replikace viru imunologie   MeSH
• vakcínie virologie   MeSH
• virové vakcíny imunologie   MeSH
• virus vakcinie genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferon typ I MeSH
• interferonový regulační faktor 3 MeSH
• interleukin-1beta MeSH
• virové vakcíny MeSH