Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism

0549782 - FGÚ 2022 RIV CH eng J - Journal Article
Pilná, H. - Hájková, V. - Knitlová, Jarmila - Lišková, Jana - Elsterová, Jana - Melková, Z.
Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism.
Viruses. Roč. 13, č. 10 (2021), č. článku 1986. E-ISSN 1999-4915
R&D Projects: GA MŠMT(CZ) LQ1604; GA TA ČR(CZ) TN01000013
Institutional support: RVO:67985823 ; RVO:60077344
Keywords : IRF-3 * vaccinia virus * smallpox * atopic dermatitis * eczema vaccinatum * immunization * interferon beta * interleukin-1 beta * cytokines * Nc/Nga mice
OECD category: Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction); Virology (BC-A)
Impact factor: 5.818, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1999-4915/13/10/1986

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.
Permanent Link: http://hdl.handle.net/11104/0325691