scholarly journals Interferon regulatory factor 7- (IRF7-) mediated immune response affects Newcastle disease virus replication in chicken embryo fibroblasts

2014 ◽  
Vol 62 (4) ◽  
pp. 500-511 ◽  
Author(s):  
Zhaoxiong Wang ◽  
Zhangyong Ning ◽  
Minhua Sun ◽  
Shimin Gao ◽  
Yinfeng Kang ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Replication ◽  
Newcastle Disease ◽  
Chicken Embryo ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7 ◽  
Kinetics Of ◽  
Chicken Embryo Fibroblasts

Interferon regulatory factor 7 (IRF7) is essential for the induction of an antiviral response. Previous studies have shown that virus replication causes the activation or expression of Type I interferon (IFN) in cells, which further activates IFN-stimulated genes (ISGs) to retard virus growth. In this study, after infection of chicken embryo fibroblasts (CEFs) with the lentogenic Newcastle disease virus (NDV) strain LaSota or the velogenic NDV strain GM, the mRNA and protein levels of IRF7 showed a significant increase, and part of the IRF7 protein was translocated from the cytoplasm to the nucleus. In order to further explore the effect of IRF7-mediated innate immune response on the replication of NDV in CEFs, the mRNA levels of IFN-α, IFN-β and STAT1 were measured and the replication kinetics of NDV determined. The results showed that specific siRNA could inhibit the expression of IRF7 and limit the mRNA level of IFN-α, IFN-β and STAT1 and, accordingly, the replication kinetics of both NDVs were enhanced after the inhibition of IRF7. In conclusion, IRF7 is an important nuclear transcription factor for the induction of Type I IFNs during the antiviral response, which can affect the replication of NDV and spread to CEFs in the early phase of viral infection.

scholarly journals DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein

2021 ◽  
Vol 12 ◽  
Author(s):  
Yalan Lai ◽  
Xiaoyan Xia ◽  
Anchun Cheng ◽  
Mingshu Wang ◽  
Xumin Ou ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Viral Protein ◽  
Interferon Regulatory Factor ◽  
Host Cells ◽  
Luciferase Reporter ◽  
Type I ◽  
Dependent Manner ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7

Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-β by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-β-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.

scholarly journals miR-541-3p Promoted Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) Replication by Targeting Interferon Regulatory Factor 7

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 126
Author(s):  
Xibao Shi ◽  
Yuanhao Yang ◽  
Xiaozhuan Zhang ◽  
Xiaobo Chang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Respiratory Syndrome Virus ◽  
Type I ◽  
Regulatory Factor ◽  
Prrs Virus ◽  
Interferon Regulatory Factor 7 ◽  
Host Innate Immune Response ◽  
And Control

Porcine reproductive and respiratory syndrome (PRRS) is a disease caused by PRRS virus (PRRSV), which seriously harms the pig industry. Revealing the mechanism by which PRRSV inhibits immune response will help prevent and control PRRS. Here, we found that PRRSV-2 may hijack host miR-541-3p to inhibit host innate immune response. Firstly, this work showed that miR-541-3p mimics could facilitate the replication of PRRSV-2 and the results of the quantitative real time polymerase chain reaction (qRT-PCR) showed that PRRSV-2 could up-regulate the expression of miR-541-3p in MARC-145 cells. Since previous studies have shown that type I interferon could effectively inhibit the replication of PRRSV-2, the present work explored whether miR-541-3p regulated the expression of type I interferon and found that miR-541-3p could negatively regulate the transcription of type I interferon by targeting interferon regulatory factor 7 (IRF7). More importantly, PRRSV-2 infection could down-regulate the expression of IRF7 and over-expression of IRF7 could down-regulate the replication of PRRSV-2 in MARC-145 cells. In conclusion, PRRSV-2 infection up-regulated the expression of miR-541-3p to promote its replication in MARC-145 cells, since miR-541-3p can negatively regulate the transcription of type I interferon by targeting IRF7.

scholarly journals Interferon regulatory factor 7 (IRF7) represents a link between inflammation and fibrosis in the pathogenesis of systemic sclerosis

2019 ◽  
Vol 78 (11) ◽  
pp. 1583-1591 ◽  
Author(s):  
Minghua Wu ◽  
Brian Skaug ◽  
Xiongjie Bi ◽  
Tingting Mills ◽  
Gloria Salazar ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interferon Regulatory Factor ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Type I Ifn ◽  
Hydroxyproline Content ◽  
Regulatory Factor ◽  
Dermal Fibrosis ◽  
Interferon Regulatory Factor 7

ObjectivesThere is considerable evidence that implicates dysregulation of type I interferon signalling (or type I IFN signature) in the pathogenesis of systemic sclerosis (SSc). Interferon regulatory factor 7 (IRF7) has been recognised as a master regulator of type I IFN signalling. The objective of this study was to elucidate the role of IRF7 in dermal fibrosis and SSc pathogenesis.MethodsSSc and healthy control skin biopsies were investigated to determine IRF7 expression and activation. The role of IRF7 in fibrosis was investigated using IRF7 knockout (KO) mice in the bleomycin-induced and TSK/+mouse models. In vitro experiments with dermal fibroblasts from patients with SSc and healthy controls were performed.ResultsIRF7 expression was significantly upregulated and activated in SSc skin tissue and explanted SSc dermal fibroblasts compared with unaffected, matched controls. Moreover, IRF7 expression was stimulated by IFN-α in dermal fibroblasts. Importantly, IRF7 co-immunoprecipitated with Smad3, a key mediator of transforming growth factor (TGF)-β signalling, and IRF7 knockdown reduced profibrotic factors in SSc fibroblasts. IRF7 KO mice demonstrated attenuated dermal fibrosis and inflammation compared with wild-type mice in response to bleomycin. Specifically, hydroxyproline content, dermal thickness as well as Col1a2, ACTA2 and interleukin-6 mRNA levels were significantly attenuated in IRF7 KO mice skin tissue. Furthermore, IRF7 KO in TSK/+mice attenuated hydroxyproline content, subcutaneous hypodermal thickness, Col1a2 mRNA as well as α-smooth muscle actin and fibronectin expression.ConclusionsIRF7 is upregulated in SSc skin, interacts with Smad3 and potentiates TGF-β-mediated fibrosis, and therefore may represent a promising therapeutic target in SSc.

The role of interferon regulatory factor 7 in the pathogenicity and immunogenicity of rabies virus in a mouse model

2021 ◽  
Vol 102 (10) ◽  
Author(s):  
Caiqian Wang ◽  
Lei Lv ◽  
Qiong Wu ◽  
Zongmei Wang ◽  
Zhaochen Luo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rabies Virus ◽  
Plasma Cells ◽  
Early Stage ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Type I Ifn ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7

Rabies is a zoonotic disease caused by the rabies virus (RABV). RABV can lead to fatal encephalitis and is still a serious threat in most parts of the world. Interferon regulatory factor 7 (IRF7) is the main transcriptional regulator of type I IFN, and it is crucial for the induction of IFNα/β and the type I IFN-dependent immune response. In this study, we focused on the role of IRF7 in the pathogenicity and immunogenicity of RABV using an IRF7-/- mouse model. The results showed that the absence of IRF7 made mice more susceptible to RABV, because IRF7 restricted the replication of RABV in the early stage of infection. IRF7 deficiency affected the recruitment of plasmacytoid dendritic cells to the draining lymph nodes (dLNs), reduced the production of type I IFN and expression of IFN-stimulated genes. Furthermore, we found that the ability to produce specific RABV-neutralizing antibody was impaired in IRF7-/- mice. Consistently, IRF7 deficiency affected the recruitment of germinal-centre B cells to dLNs, and the generation of plasma cells and RABV-specific antibody secreting cells. Moreover, the absence of IRF7 downregulated the induction of IFN-γ and reduced type 1 T helper cell (Th1)-dependent antibody production. Collectively, our findings demonstrate that IRF7 promotes humoral immune responses and compromises the pathogenicity of RABV in a mouse model.

scholarly journals Interferon Regulatory Factor 7 Attenuates Chronic Gammaherpesvirus Infection

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
K. E. Johnson ◽  
C. A. Aurubin ◽  
C. N. Jondle ◽  
P. T. Lange ◽  
V. L. Tarakanova
Keyword(s):  
Transcription Factor ◽  
Peritoneal Cavity ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Viral Reactivation ◽  
Type I ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7 ◽  
Antiviral Role

ABSTRACT Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and are associated with a variety of malignancies, including lymphomas. Interferon regulatory factor 7 (IRF-7) is an innate immune transcription factor that restricts acute replication of diverse viruses, including murine gammaherpesvirus 68 (MHV68). Importantly, very little is known about the role of IRF-7 during chronic virus infections. In this study, we demonstrate that IRF-7 attenuates chronic infection by restricting establishment of gammaherpesvirus latency in the peritoneal cavity and, to a lesser extent, viral reactivation in the spleen. Despite the classical role of IRF-7 as a stimulator of type I interferon (IFN) transcription, there were no global effects on the expression of IFN-induced genes (ISGs) in the absence of IRF-7, with only a few ISGs showing attenuated expression in IRF-7-deficient peritoneal cells. Further, IRF-7 expression was dispensable for the induction of a virus-specific CD8 T cell response. In contrast, IRF-7 expression restricted latent gammaherpesvirus infection in the peritoneal cavity under conditions where the viral latent reservoir is predominantly hosted by peritoneal B cells. This report is the first demonstration of the antiviral role of IRF-7 during the chronic stage of gammaherpesvirus infection. IMPORTANCE The innate immune system of the host is critical for the restriction of acute viral infections. In contrast, the role of the innate immune network during chronic herpesvirus infection remains poorly defined. Interferon regulatory factor 7 (IRF-7) is a transcription factor with many target genes, including type I interferons (IFNs). In this study, we show that the antiviral role of IRF-7 continues into the chronic phase of gammaherpesvirus infection, wherein IRF-7 restricts the establishment of viral latency and viral reactivation. This study is, to our knowledge, the first to define the role of IRF-7 in chronic virus infection.

Differential Expression of Cow Innate and Adaptive Responses Genes in Response to Eugenol

2021 ◽  
Vol 99 (Supplement_2) ◽  
pp. 31-32
Author(s):  
Mulumebet worku ◽  
Bahrath Kumar ◽  
Hamid Ismail
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Regulation Of Gene Expression ◽  
Interferon Regulatory Factor ◽  
Farm Animals ◽  
Type I ◽  
Regulatory Factor ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Interferon Regulatory Factor 7

Abstract Dietary phytochemicals have both nutritional and health benefits for farm animals. Research on the immunomodulatory effects of phytochemicals may aid in developing novel therapeutic agents and provide insights into the regulation of gene expression. Eugenol (4-allyl-2-methoxyphenyl) is the active ingredient in clove oil that has been studied for its immunomodulatory/anti-inflammatory effects. The objective of this study was to evaluate the effect of eugenol on the expression of genes associated with the cow’s innate and adaptive immune responses. Blood was collected from (n = 3) clinically healthy Holstein-Friesian cows from the North Carolina A&T State University Dairy Unit. One milliliter of whole blood from three cows was treated individually with 10 ng/mL of Eugenol (Sigma-Aldrich St. Louis, MO), or maintained in PBS, incubated at 37ºC for 30 minutes. Total RNA was extracted, reverse transcribed, and real-time PCR was carried out using the RT2 Profiler™ human Innate & Adaptive Immune Responses PCR Array containing 84 genes, as recommended by the manufacturer (Qiagen). The Livak method was used to calculate fold change (FC >2 considered significant). The analysis showed that 25 genes out of 84 genes were affected by treatment with eugenol. Among 25 genes, 19 were upregulated, and 2 genes were downregulated. The highest up-regulated and down-regulated genes following exposure to eugenol was IL23A and Interferon Regulatory Factor 7 (IRF7), respectively. The upregulation of the IL-23A gene expression by exogenous eugenol may be important in the production of pro-inflammatory cytokines and warrants further studies to investigate the mechanism involved. Interferon Regulatory Factor 7 is a critical regulator of type I interferon production and plays an important role in innate immune responses. The observed transcriptional expression of IL23A and IRF7 by eugenol provides an insight into immune modulation in cow blood.

Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance

2013 ◽  
Vol 305 (4) ◽  
pp. E485-E495 ◽  
Author(s):  
Xin-An Wang ◽  
Ran Zhang ◽  
Shumin Zhang ◽  
Shan Deng ◽  
Dingsheng Jiang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Multiple Organs ◽  
Interferon Regulatory Factor 7

Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of interferon regulatory factor 7 (IRF7), a master regulator of type I interferon-dependent immune responses, in the regulation of energy metabolism. The expression levels of IRF7 were increased in white adipose tissue, liver tissue, and gastrocnemius muscle of both diet-induced obese mice and ob/ ob mice compared with their lean counterparts. After feeding a high-fat diet (HFD) for 24 wk, IRF7 knockout (KO) mice showed less weight gain and adiposity than wild-type controls. KO of IRF7 improved glucose and lipid homeostasis and insulin sensitivity. Additionally, KO of IRF7 ameliorated diet-induced hepatic steatosis. Next, we assessed the inflammatory state of the IRF7 KO mice on the HFD. These mice showed less macrophage infiltration into multiple organs and were protected from local and systemic inflammation. This study demonstrates a role for IRF7 in diet-induced alterations in energy metabolism and insulin sensitivity. Our results also suggest that IRF7 is involved in the etiology of metabolic abnormalities, which suggests a new strategy for treating obesity and type 2 diabetes.

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