A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production
Interferon-chi (IFN-χ) is a type of function-unknown IFN. IFN-χ in bovines (BoIFN-χ) has evolved as a multigene family. This family comprises four IFN-χ subtypes, two of which are functional genes, which we demonstrated to (i) have antiviral and antiproliferative activities, (ii) be highly sensitive...
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Frontiers Media S.A.
2020-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.528854/full |
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author | Yongli Guo Yongli Guo Zhifeng Song Chenfeng Li Yueyang Yu Haiyue Dai Xiuxin Luo Yujiao Wang Junwei Wang Mingchun Gao |
author_facet | Yongli Guo Yongli Guo Zhifeng Song Chenfeng Li Yueyang Yu Haiyue Dai Xiuxin Luo Yujiao Wang Junwei Wang Mingchun Gao |
author_sort | Yongli Guo |
collection | DOAJ |
description | Interferon-chi (IFN-χ) is a type of function-unknown IFN. IFN-χ in bovines (BoIFN-χ) has evolved as a multigene family. This family comprises four IFN-χ subtypes, two of which are functional genes, which we demonstrated to (i) have antiviral and antiproliferative activities, (ii) be highly sensitive to trypsin, and (iii) remain stable with changes in pH and temperature. BoIFN-χ is a key intermediate in antiviral response, PAbs against BoIFN-χs could downregulate the transcriptional activation of ISGs induced by poly(I:C), and BoIFN-χs could be induced upon virus infection at the early and late phase. Additionally, BoIFN-χs bind with type-I IFN receptors, induce transcription of interferon regulatory factor 7 (IRF7), interferon-stimulated genes (ISGs), and type-I IFNs as well as myxovirus resistance protein 1 (Mx1) expression. Expression of ISGs and activation of IFN-stimulated response element (ISRE) induced with BoIFN-χs could be downregulated significantly by the Janus kinase (JAK) 1 and signal transducers and activators of transcription (STAT) 1 inhibitor. The promoters of BoIFN-β, nuclear factor-kappa B, and ISRE could be activated with BoIFN-χs, and the BoIFN-χ promoter could be activated by other type-I IFNs. Overall, BoIFN-χ could be induced with virus infection and signal through the JAK-STAT pathway to form a positive-feedback regulation of IFN production. These findings may facilitate further research on the role of IFN-χ in innate immune responses. |
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language | English |
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publishDate | 2020-10-01 |
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series | Frontiers in Immunology |
spelling | doaj.art-e40f470e979745c7992e64d6a2bde77f2022-12-21T23:57:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.528854528854A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon ProductionYongli Guo0Yongli Guo1Zhifeng Song2Chenfeng Li3Yueyang Yu4Haiyue Dai5Xiuxin Luo6Yujiao Wang7Junwei Wang8Mingchun Gao9College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaAnimal Disease Prevention and Control Center of Heilongjiang Province, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaInterferon-chi (IFN-χ) is a type of function-unknown IFN. IFN-χ in bovines (BoIFN-χ) has evolved as a multigene family. This family comprises four IFN-χ subtypes, two of which are functional genes, which we demonstrated to (i) have antiviral and antiproliferative activities, (ii) be highly sensitive to trypsin, and (iii) remain stable with changes in pH and temperature. BoIFN-χ is a key intermediate in antiviral response, PAbs against BoIFN-χs could downregulate the transcriptional activation of ISGs induced by poly(I:C), and BoIFN-χs could be induced upon virus infection at the early and late phase. Additionally, BoIFN-χs bind with type-I IFN receptors, induce transcription of interferon regulatory factor 7 (IRF7), interferon-stimulated genes (ISGs), and type-I IFNs as well as myxovirus resistance protein 1 (Mx1) expression. Expression of ISGs and activation of IFN-stimulated response element (ISRE) induced with BoIFN-χs could be downregulated significantly by the Janus kinase (JAK) 1 and signal transducers and activators of transcription (STAT) 1 inhibitor. The promoters of BoIFN-β, nuclear factor-kappa B, and ISRE could be activated with BoIFN-χs, and the BoIFN-χ promoter could be activated by other type-I IFNs. Overall, BoIFN-χ could be induced with virus infection and signal through the JAK-STAT pathway to form a positive-feedback regulation of IFN production. These findings may facilitate further research on the role of IFN-χ in innate immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2020.528854/fullbovine IFN-χmolecular characterizationantiviral activityJAK-STAT signaling pathwaypositive feedback regulation |
spellingShingle | Yongli Guo Yongli Guo Zhifeng Song Chenfeng Li Yueyang Yu Haiyue Dai Xiuxin Luo Yujiao Wang Junwei Wang Mingchun Gao A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production Frontiers in Immunology bovine IFN-χ molecular characterization antiviral activity JAK-STAT signaling pathway positive feedback regulation |
title | A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production |
title_full | A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production |
title_fullStr | A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production |
title_full_unstemmed | A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production |
title_short | A Novel Type-I Interferon Family, Bovine Interferon-Chi, Is Involved in Positive-Feedback Regulation of Interferon Production |
title_sort | novel type i interferon family bovine interferon chi is involved in positive feedback regulation of interferon production |
topic | bovine IFN-χ molecular characterization antiviral activity JAK-STAT signaling pathway positive feedback regulation |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.528854/full |
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