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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Main Authors: Yongli Guo, Zhifeng Song, Chenfeng Li, Yueyang Yu, Haiyue Dai, Xiuxin Luo, Yujiao Wang, Junwei Wang, Mingchun Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Immunology
Subjects:
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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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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