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.

• Keywords
• IRF-3, Nc/Nga mice, atopic dermatitis, cytokines, eczema vaccinatum, immunization, interferon beta, interleukin-1 beta, smallpox, vaccinia virus,
• MeSH
• Gene Expression genetics   MeSH
• Immunity immunology   MeSH
• Poxviridae Infections immunology   prevention & control   MeSH
• Interferon Type I metabolism   MeSH
• Interferon Regulatory Factor-3 genetics   immunology   MeSH
• Interleukin-1beta immunology   MeSH
• Skin immunology   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Poxviridae pathogenicity   MeSH
• Gene Expression Regulation, Viral genetics   MeSH
• Virus Replication immunology   MeSH
• Vaccinia virology   MeSH
• Viral Vaccines immunology   MeSH
• Vaccinia virus genetics   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interferon Type I MeSH
• Interferon Regulatory Factor-3 MeSH
• Interleukin-1beta MeSH
• Viral Vaccines MeSH