Induction of type I interferon genes and interferon-inducible genes in embryonal stem cells devoid of interferon regulatory factor 1.

ABSTRACT Gammaherpesviruses are ubiquitous pathogens that establish lifelong infection in >95% of adults worldwide and are associated with a variety of malignancies. Coevolution of gammaherpesviruses with their hosts has resulted in an intricate relationship between the virus and the host immune system, and perturbation of the virus-host balance results in pathology. Interferon regulatory factor 1 (IRF-1) is a tumor suppressor that is also involved in the regulation of innate and adaptive immune responses. Here, we show that type I interferon (IFN) and IRF-1 cooperate to control acute gammaherpesvirus infection. Specifically, we demonstrate that a combination of IRF-1 and type I IFN signaling ensures host survival during acute gammaherpesvirus infection and supports IFN gamma-mediated suppression of viral replication. Thus, our studies reveal an intriguing cross talk between IRF-1 and type I and II IFNs in the induction of the antiviral state during acute gammaherpesvirus infection. IMPORTANCE Gammaherpesviruses establish chronic infection in a majority of adults, and this long-term infection is associated with virus-driven development of a range of malignancies. In contrast, a brief period of active gammaherpesvirus replication during acute infection of a naive host is subclinical in most individuals. Here, we discovered that a combination of type I interferon (IFN) signaling and interferon regulatory factor 1 (IRF-1) expression is required to ensure survival of a gammaherpesvirus-infected host past the first 8 days of infection. Specifically, both type I IFN receptor and IRF-1 expression potentiated antiviral effects of type II IFN to restrict gammaherpesvirus replication in vivo, in the lungs, and in vitro, in primary macrophage cultures.

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Faculty Opinions recommendation of The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1090835.544169 ◽

2007 ◽

Author(s):

Kathryn Calame

Keyword(s):

Dendritic Cells ◽

Type I Interferon ◽

Interferon Regulatory Factor ◽

Type I ◽

Regulatory Factor ◽

Interferon Induction ◽

Feedback Phase

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Chicken interferon regulatory factor 7 (IRF7) can control ALV-J virus infection by triggering type I interferon production through affecting genes related with innate immune signaling pathway

Developmental & Comparative Immunology ◽

10.1016/j.dci.2021.104026 ◽

2021 ◽

Vol 119 ◽

pp. 104026

Author(s):

Yan Wang ◽

Fuling Yang ◽

Huadong Yin ◽

Qijian He ◽

Yuxiang Lu ◽

...

Keyword(s):

Type I Interferon ◽

Interferon Regulatory Factor ◽

Innate Immune ◽

Type I ◽

Interferon Production ◽

Regulatory Factor ◽

Innate Immune Signaling ◽

Immune Signaling Pathway ◽

Interferon Regulatory Factor 7 ◽

Innate Immune Signaling Pathway

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Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses

BioMed Research International ◽

10.1155/2018/2739830 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yongxiang Liu ◽

Xiaoxiao Liu ◽

Hongtao Kang ◽

Xiaoliang Hu ◽

Jiasen Liu ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Interferon Regulatory Factor ◽

Feline Calicivirus ◽

Type I ◽

Norwalk Virus ◽

Regulatory Factor ◽

Feline Panleukopenia Virus ◽

Protein Levels ◽

Interferon Regulatory Factor 1

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

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Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system

Molecular and Cellular Biology ◽

10.1128/mcb.14.2.1500-1509.1994 ◽

1994 ◽

Vol 14 (2) ◽

pp. 1500-1509

Author(s):

H Harada ◽

E Takahashi ◽

S Itoh ◽

K Harada ◽

T A Hori ◽

...

Keyword(s):

Gene Network ◽

Interferon Regulatory Factor ◽

Chromosomal Mapping ◽

Human Interferon ◽

Type I ◽

Regulatory Factor ◽

Nf Kappa B ◽

Interferon Regulatory Factor 1 ◽

Two Factors ◽

Dna Binding Factors

Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; the former functions as a transcriptional activator, and the latter represses IRF-1 function by competing for the same cis elements. More recent studies have revealed new roles of the two factors in the regulation of cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities, respectively. In this study, we determined the structures and chromosomal locations of the human IRF-1 and IRF-2 genes and further characterized the promoters of the respective genes. Comparison of exon-intron organization of the two genes revealed a common evolutionary structure, notably within the exons encoding the N-terminal portions of the two factors. We confirmed the chromosomal mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to 4q35.1, using fluorescence in situ hybridization. The 5' regulatory regions of both genes contain highly GC-rich sequences and consensus binding sequences for several known transcription factors, including NF-kappa B. Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRF-2 gene was affected by both transient and stable IRF-1 expression. In addition, one potential IFN-gamma-activated sequence was found within the IRF-1 promoter. Thus, these results may shed light on the complex gene network involved in regulation of the IFN system.

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