A5003682597- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- Viral Infections and Vectors
- RNA regulation and disease
- Virus-based gene therapy research
- T-cell and Retrovirus Studies
- Herpesvirus Infections and Treatments
- Prostate Cancer Treatment and Research
- Influenza Virus Research Studies
- Animal Virus Infections Studies
- Animal Disease Management and Epidemiology
- HIV Research and Treatment
- Inflammasome and immune disorders
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Vector-Borne Animal Diseases
- Mosquito-borne diseases and control
- Immunotherapy and Immune Responses
- Hormonal and reproductive studies
- SARS-CoV-2 and COVID-19 Research
- Viral-associated cancers and disorders
- Hepatitis C virus research
McGill University
2015-2024
Jewish General Hospital
2014-2024
Terry Fox Research Institute
2002-2013
University of Arkansas for Medical Sciences
2011
Chosun University
2011
Bipar
2009
Royal Victoria Hospital
2009
Molecular Oncology (United States)
1994-2006
Université de Montréal
1997-2006
Université Libre de Bruxelles
2005
Rapid induction of type I interferon expression, a central event in establishing the innate antiviral response, requires cooperative activation numerous transcription factors. Although signaling pathways that activate factors nuclear factor kappaB and ATF-2/c-Jun have been well characterized, regulatory IRF-3 IRF-7 has remained critical missing link understanding signaling. We report here IkappaB kinase (IKK)-related kinases IKKepsilon TANK-binding 1 are components virus-activated...
ABSTRACTThe interferon regulatory factors (IRF) consist of a growing family related transcription proteins first identified as regulators the alpha beta (IFN-α/β) gene promoters, well interferon-stimulated response element (ISRE) some IFN-stimulated genes. IRF-3 was originally member IRF based on homology with other members and binding to ISRE ISG15 promoter. is expressed constitutively in variety tissues, relative levels mRNA do not change virus-infected or IFN-treated cells. In present...
ABSTRACT Ubiquitously expressed interferon regulatory factor 3 (IRF-3) is directly activated after virus infection and functions as a key activator of the immediate-early alpha/beta (IFN) genes, well RANTES chemokine gene. In present study, tetracycline-inducible expression system expressing constitutively active form IRF-3 (IRF-3 5D) was combined with DNA microarray analysis to identify target genes regulated by IRF-3. Changes in mRNA profiles 8,556 were monitored Tet-inducible 5D. Among...
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a novel that causes highly contagious disease, SARS, with significant mortality. Although factors contributing to the pathogenic nature of SARS-CoV remain poorly understood, it has been reported infection does not induce type I interferons (IFNs) in cell culture. However, uncertain whether evades host detection or evolved mechanisms counteract innate defenses. We show here triggers weak IFN response cultured human lung/bronchial...
The nucleotide-binding oligomerization domain-like receptor (Nlrp) 6 maintains gut microbiota homeostasis and regulates antibacterial immunity. We now report a role for Nlrp6 in the control of enteric virus infection. Nlrp6(-/-) mice systemically challenged with encephalomyocarditis had similar mortality; however, gastrointestinal tract exhibited increased viral loads. orally infected mortality viremia compared controls. Similar results were observed murine norovirus 1. bound RNA via...
The transcription factor Nrf2 is a critical regulator of inflammatory responses. If and how also affects cytosolic nucleic acid sensing currently unknown. Here we identify as an important negative STING suggest link between metabolic reprogramming antiviral DNA in human cells. Here, activation decreases expression responsiveness to agonists while increasing susceptibility infection with viruses. Mechanistically, regulates by decreasing mRNA stability. Repression occurs metabolically...
Dengue virus (DENV) is a re-emerging arthropod borne flavivirus that infects more than 300 million people worldwide, leading to 50,000 deaths annually. Because dendritic cells (DC) in the skin and blood are first target for DENV, we sought investigate early molecular events involved host response primary human monocyte-derived (Mo-DC). Using genome-wide transcriptome analysis of DENV2-infected Mo-DC, three major responses were identified within hours infection - activation IRF3/7/STAT1...
The adaptor molecule stimulator of IFN genes (STING) is central to production type I IFNs in response infection with DNA viruses and presence host the cytosol. Excessive release through STING-dependent mechanisms has emerged as a driver several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), genes-associated vasculopathy onset infancy (SAVI). involvement STING these diseases points an unmet need for development agents that inhibit...
The interferon regulatory factor 3 (IRF-3) gene encodes a 55-kDa protein which is expressed constitutively in all tissues. In unstimulated cells, IRF-3 present an inactive cytoplasmic form; following Sendai virus infection, posttranslationally modified by phosphorylation at multiple serine and threonine residues located the carboxy terminus. Virus-induced of leads to nuclear translocation phosphorylated IRF-3, association with transcriptional coactivator CBP/p300, stimulation DNA binding...
The genes of the family interferon (IFN) regulatory factors (IRF) encode DNA binding transcriptional that are involved in modulation transcription IFN and interferon-induced (ISG). presence IRF sites promoter region <i>IFNA</i> <i>IFNB</i> indicates recognizing these play an important role virus-mediated induction genes. We have described a novel human gene this family, IRF-3, is constitutively expressed variety cell types. IRF-3 binds to interferon-sensitive response element (ISRE) present...
Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of alpha/beta IFN (IFN-alpha/beta) genes well RANTES chemokine gene. Using coexpression analysis, human IFNB, IFNA1, promoters were stimulated by coexpression, whereas IFNA4, IFNA7, IFNA14 preferentially induced only. Chimeric proteins containing combinations different domains also tested, results provided evidence distinct DNA binding properties IRF-7, a preferential association with...
Localized and systemic cytokine production in virus-infected cells play an important role the outcome of viral infection pathogenicity. Activation interferon regulatory factors (IRF) turn is a critical mediator gene transcription. Recent studies have focused on 55-kDa IRF-3 product as direct transcriptional regulator type 1 (IFN-alpha IFN-beta) activation response to virus infection. Virus induces phosphorylation specific C-terminal serine residues permits cytoplasmic-to-nuclear...
ABSTRACT Virus infection induces a rapid cellular response in cells characterized by the induction of interferon. While interferon itself does not induce an antiviral response, it activates number interferon-stimulated genes that collectively function to inhibit virus replication and spread. Previously, we others reported herpes simplex type 1 (HSV-1) -independent absence replication. Here, report HSV-1 proteins ICP0 vhs concert disable host response. In particular, show blocks regulatory...
The family of interferon (IFN) regulatory factors (IRFs) encodes DNA-binding transcription factors, some which function as modulators virus-induced signaling. IRF-3 gene is constitutively expressed in many tissues and cell types, neither virus infection nor IFN treatment enhances its transcription. In infected cells, however, protein phosphorylated at the carboxyl terminus, facilitates binding to CBP/p300 coactivator. present study, we demonstrate that overexpression significantly...
Recent studies implicate the interferon regulatory factors (IRF), IRF-3 and IRF-7, as key activators of Type 1 genes, well RANTES (regulated on activation normal T cell expressed) chemokine gene. Both IRF-7 are regulated in part by virus-induced C-terminal phosphorylation, leading to nuclear translocation, stimulation DNA binding, transcriptional activities. Structure-function with suggested a complex organization region, constitutive domain located between amino acids 150–246, an accessory...
Abstract Virus infection of host cells activates a set cellular genes, including cytokines, IFNs, and chemokines, involved in antiviral defense immune activation. Previous studies demonstrated that virus-induced transcriptional activation member the human CC-chemokine RANTES required latent transcription factors IFN-regulatory factor (IRF)-3 NF-κB via posttranslational phosphorylation. In present study, we further characterized regulatory control during virus using vivo genomic footprinting...
ABSTRACT Intracellular RNA virus infection is detected by the cytoplasmic helicase RIG-I that plays an essential role in signaling to host antiviral response. Recently, adapter molecule links sensing of incoming viral downstream and gene activation events was characterized four different groups; MAVS/IPS-1-1/VISA/Cardif contains amino-terminal CARD domain a carboxyl-terminal mitochondrial transmembrane sequence localizes membrane. Furthermore, hepatitis C NS3-4A protease complex specifically...
Activation of the interferon regulatory factors (IRFs) 3 and 7 transcription is essential for induction type I (IFN) development innate antiviral response. Retinoic acid-inducible gene has been shown to contribute virus-induced IFN production independent Toll-like receptor pathways in response a variety RNA viruses double-stranded RNA. In present study, we demonstrate that NF-kappaB-inducible, anti-apoptotic protein A20 efficiently blocks RIG-I-mediated activation NF-kappaB-, IRF-3-,...
The NF-kappaB/Rel transcription factors participate in the activation of immune system regulatory genes and viral early including human immunodeficiency virus type 1 long terminal repeat. proteins are coupled to inhibitory molecules, collectively termed IkappaB, which responsible for cytoplasmic retention NF-kappaB. Cell leads phosphorylation degradation IkappaBalpha, permitting NG-kappaB/Rel translocation nucleus target gene activation. To further characterize signaling events that...