Identification and functional analysis of two interferon regulatory factor 3 genes and their involvement in antiviral immune responses in the Chinese giant salamander Andrias davidianus

2020 ◽  
Vol 110 ◽  
pp. 103710
Author(s):  
Ya-Ping Xu ◽  
Lan-Zhi Wang ◽  
Yi-Lian Zhou ◽  
Yi Xiao ◽  
Wen-Bin Gu ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Immune Responses ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Andrias Davidianus ◽  
Chinese Giant Salamander

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

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1986
Author(s):  
Hana Pilna ◽  
Vera Hajkova ◽  
Jarmila Knitlova ◽  
Jana Liskova ◽  
Jana Elsterova ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Viral Infections ◽  
Type I Interferon ◽  
Lethal Dose ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Virus Growth

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.

scholarly journals Ipr1 Regulation by Cyclic GMP-AMP Synthase/Interferon Regulatory Factor 3 and Modulation of Irgm1 Expression via p53

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Fayang Liu ◽  
Hongni Xue ◽  
Jie Ke ◽  
Yongyan Wu ◽  
Kezhen Yao ◽  
...  
Keyword(s):  
Cyclic Gmp ◽  
Viral Infections ◽  
Pathogen Resistance ◽  
Interferon Regulatory Factor ◽  
Intracellular Pathogen ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Promoter Characterization ◽  
Ribosomal Protein L11 ◽  
Pathogenic Infection

ABSTRACT Intracellular pathogen resistance 1 (Ipr1) has been found to be a mediator to integrate cyclic GMP-AMP synthase (cGAS)–interferon regulatory factor 3 (IRF3), activated by intracellular pathogens, with the p53 pathway. Previous studies have shown the process of Ipr1 induction by various immune reactions, including intracellular bacterial and viral infections. The present study demonstrated that Ipr1 is regulated by the cGAS-IRF3 pathway during pathogenic infection. IRF3 was found to regulate Ipr1 expression by directly binding the interferon-stimulated response element motif of the Ipr1 promoter. Knockdown of Ipr1 decreased the expression of immunity-related GTPase family M member 1 (Irgm1), which plays critical roles in autophagy initiation. Irgm1 promoter characterization revealed a p53 motif in front of the transcription start site. P53 was found to participate in regulation of Irgm1 expression and IPR1-related effects on P53 stability by affecting interactions between ribosomal protein L11 (RPL11) and transformed mouse 3T3 cell double minute 2 (MDM2). Our results indicate that Ipr1 integrates cGAS-IRF3 with p53-modulated Irgm1 expression.

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