scholarly journals 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

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

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.

Abstract 1407: Interferon Regulatory Factor-9 (irf-9) Mediates Short Term Host Protection, But Promotes Long Term Immune Injury In Evolution Of Myocarditis Leading To Dilated Cardiomyopathy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Michael Konviser ◽  
Youan Liu ◽  
Manyin Chen ◽  
Yu Shi ◽  
Mei Sun ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Cardiac Hypertrophy ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Acquired Immunity ◽  
Type I ◽  
Interferon Production ◽  
Wild Type ◽  
Regulatory Factor ◽  
Host Protection

INTRODUCTION: Evolution of viral myocarditis to dilated cardiomyopathy (DCM) represents a delicate balance between host innate immunity and T-cell acquired immunity. IRF-9 is a key member of a transcription factor family that regulates type I interferon (IFN) production, critical for innate antiviral protection. However, the influence of innate immunity in general and IRF-9 in particular on acquired immunity and DCM is unknown. HYPOTHESIS: IRF-9 signaling provides immediate host protection through interferon production, but stimulates acquired immunity leading to DCM in a coxsackievirus murine myocarditis model. METHODS: Interferon-regulatory factor 9 (IRF-9) homozygous knockout mice were generated, and show impaired type I interferon production. Wild-type (WT, n=51) and IRF-9 −/− (n=124) littermates were inoculated with 10^2 p.f.u. of coxsackievirus B3 as previously described. Survival, viral titers, cardiac hypertrophy, inflammation and fibrosis were evaluated on days 0, 4, 7, 10, 14, 28 and 42. Splenocyte subpopulations were cell sorted and quantitated by FACS. RESULTS: IRF9−/− mice showed dramatically increased mortality compared to the wild-type littermates (0% WT vs 72% IRF-9 −/− on day 14, P<0.0001). On day 42, there was less cardiac hypertrophy and inflammation in IRF-9 −/− mice compared to WT controls (p<0.05). There was no difference in fibrosis. The mature T-lymphocyte population, defined as CD4 or CD8 single positive, was statistically identical in the two populations up until and including day 28 post-infection. However on day 42 there was a dramatic increase in the number of cytotoxic and helper T-Cells in the wild-type mice that was not observed in the IRF-9 −/− spleens (p<0.05). CONCLUSIONS: These data suggest a novel dual role of IRF-9 in not only regulating interferon in acute stage of viral infection in myocarditis, but also late acquired immunity activation, including CD4/8 populations, contributing to the development of chronic cardiomyopathy.

scholarly journals African swine fever virus E120R protein inhibits interferon-β production by interacting with IRF3 to block its activation

2021 ◽  
Author(s):  
Huisheng Liu ◽  
Zixiang Zhu ◽  
Tao Feng ◽  
Zhao Ma ◽  
Qiao Xue ◽  
...  
Keyword(s):  
Type I Interferon ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Interferon Regulatory Factor ◽  
Fever Virus ◽  
Type I ◽  
Interferon Production ◽  
Structural Protein ◽  
Regulatory Factor ◽  
Host Antiviral Response

African swine fever is a devastating disease of swine caused by African swine fever virus (ASFV). The pathogenesis of the disease remains largely unknown, leaving the uncontrolled spreading of the disease in many countries and regions. Here, we identified the E120R, a structural protein of ASFV, as a key virulent factor and late phase expression protein of the virus. E120R revealed an activity to suppress host antiviral response through blocking IFN-β production, and the 72-73 amino acid sites in the C-terminal domain were essential for this function. E120R interacted with the interferon regulatory factor 3 (IRF3) and interfered with the recruitment of IRF3 to TBK1, which in turn suppressed IRF3 phosphorylation, decreasing interferon production. The recombinant mutant ASFV was further constructed to confirm the claimed mechanism. The ASFV lacking the complete E120R region could not be rescued, whereas the virus could tolerate the deletion of the 72nd and 73rd residuals in the E120R (ASFV E120R-Δ72-73aa). ASFV E120R with the two amino acids deletion failed to interact with IRF3 during ASFV E120R-Δ72-73aa infection, and the viral infection highly activated IRF3 phosphorylation and induced more robust type I interferon production in comparison with its parental ASFV. An unbiased transcriptome-wide analysis of gene expression also confirmed that a considerably higher level of ISGs was detected in ASFV E120R-Δ72-73aa-infected porcine alveolar macrophages (PAMs) than that in the wildtype ASFV-infected PAMs. Together, our findings found a novel mechanism evolved by ASFV to inhibit host antiviral response and provide a new target for guiding the development of ASFV live-attenuated vaccine. IMPORTANCE African swine fever is a highly contagious animal disease affecting pig industry worldwide, which has brought enormous economic losses. The causative agent African swine fever virus (ASFV) infection causes severe immunosuppression during viral infection, attributing to serious clinical manifestation. Therefore, identification of the viral proteins involved in immunosuppression is critical for ASFV vaccine design and development. Here, for the first time, we demonstrated that E120R protein, a structural protein of ASFV, played an important role in suppression of interferon regulatory factor 3 (IRF3) phosphorylation and type I interferon production by binding to IRF3 and blocking the the recruitment of IRF3 to TBK1. Deletion of the crucial binding sites in E120R critically increased interferon response during ASFV infection. This study explored a novel antagonistic mechanism of ASFV, which is critical for guiding the development of ASFV live-attenuated vaccines.

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.

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