Revisiting IRF1-mediated antiviral innate immunity

Zhou, Hao; Tang, Yan-Dong; Zheng, Chunfu

doi:10.1016/j.cytogfr.2022.01.004

Cited by 36 publications

(29 citation statements)

References 58 publications

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“…The low basal level of IRF1 is present in the nucleus, where it maintains constitutive expression of numerous host defense genes, including MX1 and OAS2 ( 29 ). Although IRF1 is not essential for the induction of IFN-I genes ( 30 – 32 ), there is clear evidence that IRF1 suppresses the replication of various RNA viruses ( 33 , 34 ). For example, IRF1 plays a key role in host antiviral defense against Sendai virus (SeV; a paramyxovirus sensed mainly by RIG-I) and DENV (a flavivirus sensed by both RIG-I and MDA5) ( 33 , 35 , 36 ).…”

Section: Introductionmentioning

confidence: 99%

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity

Bai

Liu

et al. 2022

J Virol

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Section: Introductionmentioning

confidence: 99%

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity

Bai

Liu

et al. 2022

J Virol

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“…Additionally, the role played by CaIRF1 in the canine IFN-I signaling pathway and its antiviral function were identified. This study demonstrates that CaIRF1 activates the response of IFN-I and ISREs and shows anti-canine parvovirus type 2 virus (CPV-2) and anti-vesicular stomatitis virus (VSV) activity in vitro, which indicates that the function of CaIRF1 is evolutionarily conserved [11].…”

Section: Introductionmentioning

confidence: 74%

Molecular characterization and antiviral effects of canine interferon regulatory factor 1 (CaIRF1)

Hao

Chen

et al. 2022

BMC Vet Res

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Background Interferon regulatory factor 1 (IRF1) is an important transcription factor that activates the type I interferon (IFN-I) response and plays a vital role in the antiviral immune response. Although IRF1 has been identified in several mammals, little information related to its function in canines has been described. Results In this study, canine IRF1 (CaIRF1) was cloned. After a series of bioinformatics analyses, we found that the CaIRF1 protein structure was similar to that of other animal IRF1 proteins, including a conserved DNA-binding domain (DBD), an IRF-association domain 2 (IAD2) domain and two nuclear localization signals (NLSs). An indirect immunofluorescence assay (IFA) revealed that CaIRF1 was mainly distributed in the nucleus. Overexpression of CaIRF1 in Madin-Darby canine kidney cells (MDCK) induced high levels of interferon β (IFNβ) and IFN-stimulated response element (ISRE) promoter activation and induced interferon-stimulated gene (ISG) expression. Subsequently, we assayed the antiviral activity of CaIRF1 against vesicular stomatitis virus (VSV) and canine parvovirus type-2 (CPV-2) in MDCK cells. Overexpression of CaIRF1 effectively inhibited the viral yields of VSV and CPV-2, while knocking down of CaIRF1 expression mildly increased viral gene copies. Conclusions CaIRF1 is involved in the cellular IFN-I signaling pathway and plays an important role in the antiviral response.

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“…Interferon regulatory factor 1 (IRF1), a key transcription factor that regulates cell proliferation and immune responses, is an inducible gene of type I and type II interferon ( Dery et al, 2014 ; Zhou et al, 2022 ). To explore the effects of etoposide on IFN signaling, we examined IRF1 expression in resistant cells.…”

Section: Resultsmentioning

confidence: 99%

The oncoprotein BCL6 enables solid tumor cells to evade genotoxic stress

Liu

Juanjuan

Yuan

et al. 2022

eLife

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Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, the clinical benefits are often countered by a rapid tumor adaptive response. Here, we report that the oncoprotein B cell lymphoma 6 (BCL6) is a core component that confers solid tumor adaptive resistance to genotoxic stress. Multiple genotoxic agents promoted BCL6 transactivation, which was positively correlated with a weakened therapeutic efficacy and a worse clinical outcome. Mechanistically, we discovered that treatment with the genotoxic agent etoposide led to the transcriptional reprogramming of multiple pro-inflammatory cytokines, among which the interferon-α and interferon-γ responses were substantially enriched in resistant cells. Our results further revealed that the activation of interferon/signal transducer and activator of transcription 1 axis directly upregulated BCL6 expression. The increased expression of BCL6 further repressed the tumor suppressor PTEN and consequently enabled resistant cancer cell survival. Accordingly, targeted inhibition of BCL6 remarkably enhanced etoposide-triggered DNA damage and apoptosis both in vitro and in vivo. Our findings highlight the importance of BCL6 signaling in conquering solid tumor tolerance to genotoxic stress, further establishing a rationale for a combined approach with genotoxic agents and BCL6-targeted therapy.

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Revisiting IRF1-mediated antiviral innate immunity

Cited by 36 publications

References 58 publications

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity

Molecular characterization and antiviral effects of canine interferon regulatory factor 1 (CaIRF1)

The oncoprotein BCL6 enables solid tumor cells to evade genotoxic stress

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