IRF-3

Summary

Gene Symbol: IRF-3
Description: interferon regulatory factor 3
Alias: IIAE7, interferon regulatory factor 3
Species: human

Top Publications

  1. pmc HIV-1 evades innate immune recognition through specific cofactor recruitment
    Jane Rasaiyaah
    University College London, Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 90 Gower Street, London WC1E 6BT, UK
    Nature 503:402-5. 2013
  2. ncbi Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation
    Tsung Hsien Chang
    Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
    Microbes Infect 8:157-71. 2006
  3. pmc Vpu mediates depletion of interferon regulatory factor 3 during HIV infection by a lysosome-dependent mechanism
    Brian P Doehle
    University of Washington School of Medicine, Department of Immunology, Seattle, Washington, USA
    J Virol 86:8367-74. 2012
  4. pmc HIV-1 Vpu does not degrade interferon regulatory factor 3
    Dominik Hotter
    Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
    J Virol 87:7160-5. 2013
  5. doi The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation
    Hongxia Li
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China
    J Gen Virol 91:2947-58. 2010
  6. ncbi Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7
    Barbora Lubyova
    Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    J Biol Chem 279:7643-54. 2004
  7. ncbi Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors
    Kenya Honda
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Bunkyo ku, Tokyo 113 0033, Japan
    Immunity 25:349-60. 2006
  8. doi Epstein-Barr virus-encoded small RNA induces IL-10 through RIG-I-mediated IRF-3 signaling
    M Samanta
    Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
    Oncogene 27:4150-60. 2008
  9. pmc Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen inhibits interferon (IFN) beta expression by competing with IFN regulatory factor-3 for binding to IFNB promoter
    Nathalie Cloutier
    Laboratory of Virology, Rheumatology and Immunology Research Center, Centre Hospitalier Universitaire de Quebec Research Center and Faculty of Medicine, Laval University, Quebec City, Quebec G1V 4G2, Canada
    J Biol Chem 285:7208-21. 2010
  10. doi Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change
    Kiyohiro Takahasi
    Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N 12W 6 Kita ku, Sapporo 060 0812, Japan
    Genes Cells 15:901-10. 2010

Research Grants

  1. A quantitative proteomics approach to understand viral immune evasion strategies
    Michele E Hardy; Fiscal Year: 2010
  2. SUSAN ELAINE SWEENEY; Fiscal Year: 2015
  3. Michael David; Fiscal Year: 2014
  4. TLR4 Signaling in alcoholic liver disease
    Gyongyi Szabo; Fiscal Year: 2013
  5. Genhong Cheng; Fiscal Year: 2015
  6. Zhijian J Chen; Fiscal Year: 2015
  7. ROBERT A LAFYATIS; Fiscal Year: 2015
  8. Role of IRF3 and RXRa Crosstalk in Host Response to Viral Infections
    Genhong Cheng; Fiscal Year: 2013
  9. Anti-interferon Activity of the Arenavirus Nucleoprotein
    Luis Martinez-Sobrido; Fiscal Year: 2012
  10. Martin E Dorf; Fiscal Year: 2015

Detail Information

Publications258 found, 100 shown here

  1. pmc HIV-1 evades innate immune recognition through specific cofactor recruitment
    Jane Rasaiyaah
    University College London, Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 90 Gower Street, London WC1E 6BT, UK
    Nature 503:402-5. 2013
    ..We conclude that HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its replication, allowing evasion of innate immune sensors and induction of a cell-autonomous innate immune response in primary human macrophages. ..
  2. ncbi Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation
    Tsung Hsien Chang
    Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
    Microbes Infect 8:157-71. 2006
    ..Therefore, we suggest that JEV and DEN-2 initiate the host innate immune response through a molecular mechanism involving RIG-I/IRF-3 and PI3K/NF-kappaB signaling pathways...
  3. pmc Vpu mediates depletion of interferon regulatory factor 3 during HIV infection by a lysosome-dependent mechanism
    Brian P Doehle
    University of Washington School of Medicine, Department of Immunology, Seattle, Washington, USA
    J Virol 86:8367-74. 2012
    ..b>Interferon regulatory factor 3 (IRF3) plays a central role in PRR signaling of innate immunity to drive the expression of type I ..
  4. pmc HIV-1 Vpu does not degrade interferon regulatory factor 3
    Dominik Hotter
    Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany
    J Virol 87:7160-5. 2013
    It has been reported that HIV-1 Vpu mediates the degradation of interferon regulatory factor 3 (IRF-3) to avoid innate immune sensing...
  5. doi The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation
    Hongxia Li
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China
    J Gen Virol 91:2947-58. 2010
    ..These findings suggest that Nsp2 is likely to play an important role in subversion of IRF-3-dependent innate antiviral defences, providing a basis for elucidating the mechanisms underlying PRRSV pathogenesis...
  6. ncbi Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7
    Barbora Lubyova
    Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    J Biol Chem 279:7643-54. 2004
    ..These studies illustrate that vIRF-3 and vIRF-1 have clearly distinct functions. In addition to its co-repressor activity, vIRF-3 can also act as a transcriptional activator on genes controlled by cellular IRF-3 and IRF-7...
  7. ncbi Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors
    Kenya Honda
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Bunkyo ku, Tokyo 113 0033, Japan
    Immunity 25:349-60. 2006
    ..Here, we summarize the recent studies on IRFs, providing a paradigm of how genes are ingeniously regulated during immune responses. We also consider some evolutional aspects on the IFN-IRF system...
  8. doi Epstein-Barr virus-encoded small RNA induces IL-10 through RIG-I-mediated IRF-3 signaling
    M Samanta
    Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
    Oncogene 27:4150-60. 2008
    ..These findings suggest a new mechanism of dsRNA signaling pathway that triggers the expression of IL-10, which acts as an autocrine growth factor in BL cells...
  9. pmc Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen inhibits interferon (IFN) beta expression by competing with IFN regulatory factor-3 for binding to IFNB promoter
    Nathalie Cloutier
    Laboratory of Virology, Rheumatology and Immunology Research Center, Centre Hospitalier Universitaire de Quebec Research Center and Faculty of Medicine, Laval University, Quebec City, Quebec G1V 4G2, Canada
    J Biol Chem 285:7208-21. 2010
    ..The ability of LANA-1 to inhibit IFNB gene expression highlights a new role for this protein in cellular gene modulation and immune evasion strategies...
  10. doi Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change
    Kiyohiro Takahasi
    Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N 12W 6 Kita ku, Sapporo 060 0812, Japan
    Genes Cells 15:901-10. 2010
    ..Thus, we conclude that the phosphorylation of Ser386 is essential for activation of IRF-3...
  11. pmc Genetic dissection of interferon-antagonistic functions of rabies virus phosphoprotein: inhibition of interferon regulatory factor 3 activation is important for pathogenicity
    Martina Rieder
    Max von Pettenkofer Institute and Gene Center, Ludwig Maximilians University, D 81377 Munchen, Germany
    J Virol 85:842-52. 2011
    ..Neurovirulence of IFN-resistant RV thus correlates with the capacity of the virus to prevent activation of IRF3 and IRF7...
  12. doi Direct repression of the human IRF-3 promoter by E2F1
    Hua Guo Xu
    Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, 300 Guang Zhou Road, Nanjing, Jiangsu Province 210029, China
    Immunogenetics 63:189-96. 2011
    b>Interferon regulatory factor 3 (IRF-3) plays an important role in virus and double-stranded RNA-mediated induction of type I interferon and RANTES, DNA damage signaling, tumor suppression, and virus-induced apoptosis...
  13. pmc Identification of the synthetic cannabinoid R(+)WIN55,212-2 as a novel regulator of IFN regulatory factor 3 activation and IFN-beta expression: relevance to therapeutic effects in models of multiple sclerosis
    Eric J Downer
    Institute of Immunology, National University of Ireland Maynooth, Co Kildare, Ireland
    J Biol Chem 286:10316-28. 2011
    ....
  14. pmc A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein
    Junping Ren
    Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA
    J Gen Virol 92:2153-9. 2011
    ....
  15. pmc Induction of Noxa-mediated apoptosis by modified vaccinia virus Ankara depends on viral recognition by cytosolic helicases, leading to IRF-3/IFN-β-dependent induction of pro-apoptotic Noxa
    Pedro Eitz Ferrer
    Institute of Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany
    PLoS Pathog 7:e1002083. 2011
    ..We thus here describe a pathway leading from the detection of viral RNA during MVA infection by the cytosolic helicase-pathway, to the up-regulation of Noxa and apoptosis via IRF3 and type I IFN signalling...
  16. pmc Interferon regulatory factor 3 plays an anti-inflammatory role in microglia by activating the PI3K/Akt pathway
    Leonid Tarassishin
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA
    J Neuroinflammation 8:187. 2011
    ..In the current study, we tested the hypothesis that interferon regulatory factor 3 (IRF3), a transcription factor required for the induction of IFNβ following TLR3 or TLR4 activation, ..
  17. pmc Bunyamwera virus nonstructural protein NSs counteracts interferon regulatory factor 3-mediated induction of early cell death
    Alain Kohl
    Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom
    J Virol 77:7999-8008. 2003
    ..Screening for apoptosis pathways revealed that the proapoptotic transcription factor interferon regulatory factor 3 (IRF-3) was activated by both wild-type BUN and BUNdelNSs infection, but only wild-type BUN was able ..
  18. pmc A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts
    Anne Danielle C Chessler
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    J Immunol 181:7917-24. 2008
    ..Together, these findings identify the existence of a novel TLR-independent pathogen-sensing mechanism in immune and nonimmune cells that converges on TBK1 and IFN regulatory factor 3 for activation of IFN-beta gene expression...
  19. doi Essential role of mitochondrial antiviral signaling, IFN regulatory factor (IRF)3, and IRF7 in Chlamydophila pneumoniae-mediated IFN-beta response and control of bacterial replication in human endothelial cells
    Claudia Buss
    Division of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, Charite Universitatsmedizin Berlin, Berlin, Germany
    J Immunol 184:3072-8. 2010
    ..In conclusion, C. pneumoniae infection of endothelial cells activates an MAVS-, IRF3-, and IRF7-dependent signaling, which controls bacterial growth and might modulate development of vascular lesions...
  20. ncbi HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators
    R Lin
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec H3T IE2, Canada
    Oncogene 20:800-11. 2001
    ..These results illustrate that vIRF-1 is able to block the early stages of the IFN response to virus infection by interfering with the activation of IRF-3 responsive, immediate early IFN genes...
  21. ncbi Direct involvement of CREB-binding protein/p300 in sequence-specific DNA binding of virus-activated interferon regulatory factor-3 holocomplex
    Wakako Suhara
    Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    J Biol Chem 277:22304-13. 2002
    ..Furthermore, the critical function of these domains in virus-induced gene activation was demonstrated in vivo by using p300 mutants...
  22. ncbi Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK
    Kenrie P Y Hui
    Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
    J Immunol 182:1088-98. 2009
    ....
  23. ncbi Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1
    Tatsuya Saitoh
    Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Nat Immunol 7:598-605. 2006
    ..These results elucidate a previously unknown mechanism for controlling innate antiviral responses by negatively regulating IRF3 activity via Pin1...
  24. ncbi Activation of interferon regulatory factor 3 in response to DNA-damaging agents
    T Kim
    National Creative Research Initiative Center for Genetic Reprogramming, Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151 742, Korea
    J Biol Chem 274:30686-9. 1999
    ..These observations suggest that IRF3 plays a role in the defensive responses induced by genotoxic stress...
  25. ncbi Interferon regulatory factor-3-mediated activation of the interferon-sensitive response element by Toll-like receptor (TLR) 4 but not TLR3 requires the p65 subunit of NF-kappa
    Claudia Wietek
    Department of Biochemistry, Trinity College, Dublin, Ireland
    J Biol Chem 278:50923-31. 2003
    ..Finally, p65 promoted transactivation of gene expression by IRF-3. These results therefore indicate that IRF-3-mediated activation of the ISRE by TLR4 but not TLR3 requires the p65 subunit of NF-kappa B...
  26. ncbi Antiviral gene expression in rheumatoid arthritis: role of IKKepsilon and interferon regulatory factor 3
    Susan E Sweeney
    University of California San Diego, School of Medicine, La Jolla, CA 92093, USA
    Arthritis Rheum 56:743-52. 2007
    ..This study was designed to investigate the role of the IKK-related kinase IKKepsilon and IFN regulatory factor 3 (IRF-3) in the activation of antiviral genes in rheumatoid arthritis (RA)...
  27. pmc Binding of Kaposi's sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression
    Sylvain Lefort
    Rheumatology and Immunology Research Center, Room T1 49, 2705 Laurier Blvd, Quebec, Quebec G1V 4G2, Canada
    J Virol 81:10950-60. 2007
    ..A new role for K-bZIP as a protein involved in immune evasion is therefore uncovered...
  28. doi The major outer membrane protein of a periodontopathogen induces IFN-beta and IFN-stimulated genes in monocytes via lipid raft and TANK-binding kinase 1/IFN regulatory factor-3
    Sung Hoon Lee
    Department of Oral Microbiology and Immunology, Seoul National University, Seoul, Republic of Korea
    J Immunol 182:5823-35. 2009
    ..Our results demonstrate that MspTL, the major outer protein of T. lecithinolyticum, induced IFN-beta expression and subsequent up-regulation of IP-10 and RANTES via TBK1/IRF-3/STAT-1 signaling secondary to lipid raft activation...
  29. pmc Identification of caspase-mediated decay of interferon regulatory factor-3, exploited by a Kaposi sarcoma-associated herpesvirus immunoregulatory protein
    Cristina Aresté
    Cancer Research UK Cancer Centre, School of Cancer Sciences, Vincent Drive, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom
    J Biol Chem 284:23272-85. 2009
    ..These data provide unprecedented insight into negative regulation of IRF-3 following activation of the type I IFN antiviral response and the mechanism by which KSHV vIRF-2 inhibits this innate response...
  30. doi Characterization of the human IRF-3 promoter and its regulation by the transcription factor E2F1
    Hua Guo Xu
    Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, 300 Guang Zhou Road, 210029, Nanjing, Jiangsu Province, China
    Mol Biol Rep 37:3073-80. 2010
    b>Interferon regulatory factor 3 (IRF-3), an essential transcriptional regulator of the interferon genes, has been implicated in virus and double-stranded RNA mediated induction of IFN-α, IFN-β and RANTES, in virus-induced apoptosis and ..
  31. pmc Differential gene expression downstream of Toll-like receptors (TLRs): role of c-Src and activating transcription factor 3 (ATF3)
    Thuy Thanh Nguyen
    Department of Laboratory Medicine, Children s and Women s Health, Norwegian University of Science and Technology, N 7006 Trondheim, Norway
    J Biol Chem 285:17011-9. 2010
    ..These results demonstrate functional specificity for c-Src in TLR-stimulated responses and suggest that c-Src modulation and ATF3 activity may contribute to differential regulation of IRF-3- versus IRF-5-mediated gene expression...
  32. doi Identification of novel alternative splicing variants of interferon regulatory factor 3
    Yong Li
    Key laboratory of Carcinogenesis and Translational Research, Department of Genesis, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China
    Biochim Biophys Acta 1809:166-75. 2011
    b>Interferon regulatory factor 3 (IRF-3) plays a crucial role in host defense against viral and microbial infection as well as in cell growth regulation...
  33. doi Enhanced interferon regulatory factor 3 binding to the interleukin-23p19 promoter correlates with enhanced interleukin-23 expression in systemic lupus erythematosus
    Siobhán Smith
    Royal College of Surgeons in Ireland, Dublin, Ireland
    Arthritis Rheum 64:1601-9. 2012
    To examine the role of interferon regulatory factor 3 (IRF-3) in the regulation of interleukin-23 (IL-23) production in patients with systemic lupus erythematosus (SLE).
  34. pmc Phospholipase Cγ-2 and intracellular calcium are required for lipopolysaccharide-induced Toll-like receptor 4 (TLR4) endocytosis and interferon regulatory factor 3 (IRF3) activation
    Chih Yuan Chiang
    Division of Biological Sciences, University of California, San Diego, California 92093, USA
    J Biol Chem 287:3704-9. 2012
    ..is unique among the TLRs in its use of multiple adaptor proteins leading to activation of both the interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) pathways...
  35. pmc Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein
    Megan H Orzalli
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:E3008-17. 2012
    ..Together these results define a pathway for nuclear innate sensing of HSV DNA by IFI16 in infected HFF and document a mechanism by which a virus can block this nuclear innate response...
  36. ncbi Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription
    Pierre Morin
    UPR 2228 CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints Pères, Universite Paris V, 45 Rue des Saints Peres, 75270 Paris Cedex 06, France
    J Mol Biol 316:1009-22. 2002
    ....
  37. doi Expression of interferon regulatory factor 1, 3, and 7 in primary Sjögren syndrome
    Lingyan Zheng
    Department of Oral and Maxillofacial Surgery, Ninth People s Hospital, School of Medicine, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, Shanghai, China
    Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107:661-8. 2009
    ..The aim was to investigate the level of interferon regulatory factor (IRF) 1, 3, and 7 in peripheral blood cells from patients with primary Sjogren syndrome (pSS) and to determine whether and where IRF1 exists in the parotid glands of pSS...
  38. pmc Differential regulation of human papillomavirus type 8 by interferon regulatory factors 3 and 7
    Monika Oldak
    Institute of Virology, Saarland University, Kirrbergerstrasse, Building 47, 66421 Homburg Saar, Germany
    J Virol 85:178-88. 2011
    ..Our study suggests that local application of IRF-3-activating compounds might constitute an attractive novel therapeutic strategy against HPV8-associated diseases, particularly in epidermodysplasia verruciformis patients...
  39. pmc HTLV-1 evades type I interferon antiviral signaling by inducing the suppressor of cytokine signaling 1 (SOCS1)
    Stephanie Oliere
    Molecular Oncology Group, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
    PLoS Pathog 6:e1001177. 2010
    ..These observations identify a novel SOCS1 driven mechanism of evasion of the type I IFN antiviral response against HTLV-1...
  40. pmc Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7
    Leonie Unterholzner
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    PLoS Pathog 7:e1002247. 2011
    ..Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7...
  41. pmc HIV-1 Tat C-mediated regulation of tumor necrosis factor receptor-associated factor-3 by microRNA 32 in human microglia
    Ritu Mishra
    Laboratory of Neurovirology and Inflammation Biology, Centre for Cellular and Molecular Biology CCMB, Council of Scientific and Industrial Research CSIR, Uppal Road, Hyderabad 500007, India
    J Neuroinflammation 9:131. 2012
    ..HIV-1 Tat is known to be secreted from productively infected cells and can affect neighboring uninfected cells by modulating cellular gene expression in a bystander fashion...
  42. pmc Analysis of genes induced by Sendai virus infection of mutant cell lines reveals essential roles of interferon regulatory factor 3, NF-kappaB, and interferon but not toll-like receptor 3
    Christopher P Elco
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
    J Virol 79:3920-9. 2005
    ..NF-kappaB and interferon regulatory factor 3 (IRF-3), the two major transcription factors activated by virus infection, were essential for the ..
  43. ncbi Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells
    Ezra Aksoy
    Institute for Medical Immunology IMI, Universite Libre de Bruxelles, Charleroi, Belgium
    Blood 109:2887-93. 2007
    ..IFN-inducible factors elicited by lipopolysaccharide (LPS) depends on the transcriptional activity of interferon regulatory factor 3 (IRF-3) downstream of Toll-like receptor-4 (TLR4)...
  44. pmc Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer
    Daniel Panne
    Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA
    EMBO J 23:4384-93. 2004
    ..Because the binding sites overlap on the enhancer, the unit of recognition is the entire nucleotide sequence, not the individual subsites...
  45. pmc RIG-I-mediated antiviral signaling is inhibited in HIV-1 infection by a protease-mediated sequestration of RIG-I
    Mayra Solis
    Terry Fox Molecular Oncology Group, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
    J Virol 85:1224-36. 2011
    ..This study reveals a novel PR-dependent mechanism employed by HIV-1 to counteract the early IFN response to viral RNA in infected cells...
  46. pmc HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production
    Andrew N Harman
    Centre for Virus Research, Westmead Millennium Institute, Westmead, Australia
    Blood 118:298-308. 2011
    ....
  47. pmc Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta
    Zhengfan Jiang
    University of Toronto, Toronto, ON, Canada M5G 2M9
    Proc Natl Acad Sci U S A 101:3533-8. 2004
    ..Therefore, double-stranded RNA-induced TLR3/TRIF-mediated NF-kappaB and IRF3 activation diverge at TRIF...
  48. pmc Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection
    Yueh Ming Loo
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 103:6001-6. 2006
    ..HCV protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be capable of restoring this innate host response in clinical practice...
  49. ncbi Legionella pneumophila induces IFNbeta in lung epithelial cells via IPS-1 and IRF3, which also control bacterial replication
    Bastian Opitz
    Department of Internal Medicine Infectious Diseases and Pulmonary Medicine, Charite Universitatsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
    J Biol Chem 281:36173-9. 2006
    ..pneumophila in lung epithelial cells. In conclusion, we demonstrated a critical role of IPS-1, IRF3, and IFNbeta in Legionella infection of lung epithelium...
  50. ncbi Retinoic acid-inducible gene-I and interferon-beta promoter stimulator-1 augment proapoptotic responses following mammalian reovirus infection via interferon regulatory factor-3
    Geoffrey H Holm
    Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232 2581, USA
    J Biol Chem 282:21953-61. 2007
    ..Interferon-beta promoter stimulator-1 and IRF-3 are required for efficient apoptosis following reovirus infection, suggesting a common mechanism of antiviral cytokine induction and activation of the cell death response...
  51. pmc Homo-oligomerization is essential for Toll/interleukin-1 receptor domain-containing adaptor molecule-1-mediated NF-kappaB and interferon regulatory factor-3 activation
    Kenji Funami
    Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    J Biol Chem 283:18283-91. 2008
    ..Thus, full activation and formation of TICAM-1 signalosomes requires oligomerization induced at two different sites and RIP1 binding...
  52. pmc Induction of protein kinase PKR-dependent activation of interferon regulatory factor 3 by vaccinia virus occurs through adapter IPS-1 signaling
    Ping Zhang
    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA
    J Biol Chem 283:34580-7. 2008
    b>Interferon regulatory factor 3 (IRF-3) undergoes phosphorylation-induced activation in virus-infected cells and plays an important role in the antiviral innate immune response...
  53. pmc Human T cell lymphotropic virus 1 manipulates interferon regulatory signals by controlling the TAK1-IRF3 and IRF4 pathways
    Shunsuke Suzuki
    Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930 0194, Japan
    J Biol Chem 285:4441-6. 2010
    ..Together, HTLV-1 manipulates IFN signaling by regulating both positive and negative IRFs...
  54. pmc Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3 (IRF3) phosphorylation at key serine residues: a novel mechanism of IRF3 inhibition among herpesviruses
    Nandini Sen
    Department of Pediatrics, Stanford University School of Medicine, Room S356, Grant Building, 300 Pasteur Drive, Stanford, CA 94305 5208, USA
    J Virol 84:9240-53. 2010
    ..Thus, IE62 has two critical but discrete roles following VZV entry: to induce expression of VZV genes and to disarm the IFN-dependent antiviral defense through a novel mechanism that prevents IRF3 phosphorylation...
  55. pmc HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2
    Giorgio Mangino
    Department of Biology, University Roma Tre, Rome, Italy
    PLoS ONE 6:e22982. 2011
    ....
  56. doi Tom70 mediates activation of interferon regulatory factor 3 on mitochondria
    Xin Yi Liu
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Cell Res 20:994-1011. 2010
    ..Consequently, this leads to the activation of TANK-binding kinase 1 (TBK1) and phosphorylation of interferon regulatory factor 3 (IRF3), both of which constitutively associate with cytosolic chaperone Hsp90...
  57. doi The Rab11a GTPase controls Toll-like receptor 4-induced activation of interferon regulatory factor-3 on phagosomes
    Harald Husebye
    Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, N 7489 Trondheim, Norway
    Immunity 33:583-96. 2010
    ..Moreover, Rab11a silencing reduced the amount of TRAM on phagosomes. Thus, Rab11a is an important regulator of TLR4 and TRAM transport to E. coli phagosomes thereby controlling IRF3 activation from this compartment...
  58. ncbi Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3
    W C Au
    Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Virology 280:273-82. 2001
    ..Altogether these results suggest that the IRF-3/IRF-7 complexes are biologically active and are involved in virus-activated transcription of endogenous IFNA genes...
  59. ncbi The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling
    Annett Schoenemeyer
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 280:17005-12. 2005
    ..IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling...
  60. ncbi Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages
    Mayra Solis
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Canada H3T 1E2
    Biochem Pharmacol 72:1469-76. 2006
    ..These studies indicate that IRF-7 transduced macrophages may be an attractive candidate for in vivo adoptive therapy of cancer...
  61. ncbi Distinct roles for IFN regulatory factor (IRF)-3 and IRF-7 in the activation of antitumor properties of human macrophages
    Raphaelle Romieu-Mourez
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
    Cancer Res 66:10576-85. 2006
    ..In conclusion, transduction of active forms of IRF-3 or IRF-7 differentially modulate the apoptotic and antitumor properties of primary macrophages, with active IRF-7 leading to the acquisition of novel antitumor effector functions...
  62. pmc Structural and functional analysis of interferon regulatory factor 3: localization of the transactivation and autoinhibitory domains
    R Lin
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Canada H3T 1E2
    Mol Cell Biol 19:2465-74. 1999
    The interferon regulatory factor 3 (IRF-3) gene encodes a 55-kDa protein which is expressed constitutively in all tissues...
  63. pmc Regulated nuclear-cytoplasmic localization of interferon regulatory factor 3, a subunit of double-stranded RNA-activated factor 1
    K P Kumar
    Department of Pathology, SUNY at Stony Brook, Stony Brook, New York 11794, USA
    Mol Cell Biol 20:4159-68. 2000
    ..DRAF1 is a multimeric transcription factor containing the interferon regulatory factor 3 (IRF-3) protein and one of the histone acetyl transferases, CREB binding protein (CBP) or p300 (CBP/..
  64. pmc Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes
    Fumiyo Ikeda
    Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany
    EMBO J 26:3451-62. 2007
    ..We propose that the ULD is a regulatory component of the TBK1/IKK-i kinases involved in the control of the kinase activation, substrate presentation and downstream signaling pathways...
  65. doi poly(I:C) and LPS induce distinct IRF3 and NF-kappaB signaling during type-I IFN and TNF responses in human macrophages
    Thornik Reimer
    Institute of Veterinary Virology, University of Bern, Laenggassstrasse 122, Bern CH 3001, Switzerland
    J Leukoc Biol 83:1249-57. 2008
    ..Thus, in human macrophages, poly(I:C) treatment induces a distinct cytokine response when compared with murine macrophages. Additionally, a robust IFN-beta response can be induced in the absence of detectable IRF3 activation...
  66. pmc The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3
    Rowan Higgs
    Molecular and Cellular Therapeutics, Research Institute, Royal College of Surgeons in Ireland, Dublin, Ireland
    J Immunol 181:1780-6. 2008
    ..Collectively, this demonstrates a novel role for Ro52 in turning off and thus limiting IRF3-dependent type I IFN production by targeting the transcription factor for polyubiquitination and subsequent proteasomal degradation...
  67. pmc Human immunodeficiency virus type 1 mediates global disruption of innate antiviral signaling and immune defenses within infected cells
    Brian P Doehle
    University of Washington School of Medicine, Department of Immunology, Seattle, WA 98195, USA
    J Virol 83:10395-405. 2009
    b>Interferon regulatory factor 3 (IRF-3) is essential for innate intracellular immune defenses that limit virus replication, but these defenses fail to suppress human immunodeficiency virus (HIV) infection, which can ultimately associate ..
  68. pmc Viral apoptosis is induced by IRF-3-mediated activation of Bax
    Saurabh Chattopadhyay
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    EMBO J 29:1762-73. 2010
    ..Thus, IRF-3 is a dual-action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell...
  69. doi Aberrant expression of interferon regulatory factor 3 in human lung cancer
    Takayuki Tokunaga
    Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1 12 4 Sakamoto, Nagasaki 852 8523, Japan
    Biochem Biophys Res Commun 397:202-7. 2010
    We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer...
  70. pmc Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system
    Chang Shu
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas, USA
    Nat Struct Mol Biol 19:722-4. 2012
    ..Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosine, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling...
  71. ncbi Identification of the minimal phosphoacceptor site required for in vivo activation of interferon regulatory factor 3 in response to virus and double-stranded RNA
    Marc J Servant
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research and the Departments of Microbiology and Immunology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada
    J Biol Chem 278:9441-7. 2003
    ..The inability of the phosphospecific antibody to detect Ser(396) phosphorylation in lipopolysaccharide-treated cells suggests that other major pathways may be involved in IRF-3 activation following Toll-like receptor 4 stimulation...
  72. ncbi IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nat Immunol 4:491-6. 2003
    The transcription factors interferon regulatory factor 3 (IRF3) and NF-kappaB are required for the expression of many genes involved in the innate immune response...
  73. pmc Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response
    Davide A Abate
    Department of Microbiology and Immunology, D 347 Fairchild Science Bldg, Stanford University School of Medicine, Stanford, CA 94305 5124, USA
    J Virol 78:10995-1006. 2004
    ..By subverting IRF-3, the virus escapes throwing a central alarm devoted to both immediate antiviral control and regulation of the immune response...
  74. ncbi VISA is an adapter protein required for virus-triggered IFN-beta signaling
    Liang Guo Xu
    Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado 80206, USA
    Mol Cell 19:727-40. 2005
    ..These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling...
  75. pmc West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling
    Brenda L Fredericksen
    Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA
    J Virol 80:2913-23. 2006
    ..We have previously shown that West Nile virus NY (WNV-NY) delays activation of interferon regulatory factor 3 (IRF-3), a transcription factor critical to the initiation of the antiviral response...
  76. pmc Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-beta induction
    Gregory T Melroe
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Virology 360:305-21. 2007
    ..Therefore, ICP0 provides an example of how viruses can block IFN-beta induction by sequestration of important transcription factors essential for the host response...
  77. ncbi Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer
    Carlos R Escalante
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA
    Mol Cell 26:703-16. 2007
    b>Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of the mammalian interferon-beta (IFN-beta) enhanceosome...
  78. pmc S-glutathionylation of IRF3 regulates IRF3-CBP interaction and activation of the IFN beta pathway
    Efthimios Prinarakis
    Center of Basic Research I Biochemistry Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece
    EMBO J 27:865-75. 2008
    b>Interferon regulatory factor 3 (IRF3) is an essential transcriptional regulator of the interferon genes. IRF3 is constitutively present in a latent conformation in the cell cytoplasm...
  79. doi Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus
    M Akahoshi
    Laboratory for Genetics of Allergic Diseases, SNP Research Center, RIKEN Yokohama Institute, The Institute of Physical and Chemical Research RIKEN, Yokohama, Japan
    Lupus 17:568-74. 2008
    ..In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE...
  80. pmc The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response
    Didier Soulat
    Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria
    EMBO J 27:2135-46. 2008
    ..Phosphorylation-deficient mutants of DDX3X failed to synergize with TBK1 in their ability to stimulate the IFN promoter. Overall, our data imply that DDX3X is a critical effector of TBK1 that is necessary for type I IFN induction...
  81. doi The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation
    Bo Zhong
    College of Life Sciences, Wuhan University, Wuhan 430072, China
    Immunity 29:538-50. 2008
    ..Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity...
  82. pmc Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7
    Pierre Genin
    UPR 2228 CNRS, Laboratoire de Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints Pères, Universite Paris Descartes, 45 Rue des Saints Peres, 75270 Paris Cedex 06, France
    Mol Cell Biol 29:3435-50. 2009
    ..IFN-A) gene cluster is modulated following paramyxovirus infection by the relative amounts of active interferon regulatory factor 3 (IRF-3) and IRF-7...
  83. doi Infection with herpes simplex type 1-based amplicon vectors results in an IRF3/7-dependent, TLR-independent activation of the innate antiviral response in primary human fibroblasts
    Eliza Tsitoura
    Universite de Lyon, F 69003, Lyon, France
    J Gen Virol 90:2209-20. 2009
    ..Therefore, our results confirm the existence of TLR-independent, IRF3/7-dependent activation pathways triggered by HSV-1 particles in human fibroblasts...
  84. pmc TLR3 and TLR4 are innate antiviral immune receptors in human microglia: role of IRF3 in modulating antiviral and inflammatory response in the CNS
    Hyeon Sook Suh
    Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Virology 392:246-59. 2009
    ..We suggest that a balanced expression between inflammatory and innate immune genes might be achieved by IRF3 over-expression...
  85. pmc The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3
    Hwijin Kim
    Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Nat Immunol 11:743-50. 2010
    ..Higher expression of MafB in human pancreatic islet beta cells might increase cellular vulnerability to viral infections associated with the etiology of type 1 diabetes...
  86. doi Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1
    Sun Myung Joung
    School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea
    J Immunol 186:499-507. 2011
    ..To our knowledge, our results demonstrate a new regulatory mechanism for Akt activation mediated by TBK1 and a novel role of Akt in TLR-mediated immune responses...
  87. pmc STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway
    Yasuo Tanaka
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Sci Signal 5:ra20. 2012
    ..adaptor protein STING (stimulator of IFN genes), which activates the transcription factor interferon regulatory factor 3 (IRF3); however, how STING activates IRF3 is unclear...
  88. pmc Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1
    B K Weaver
    Department of Pathology, State University of New York at Stony Brook, 11794, USA
    Mol Cell Biol 18:1359-68. 1998
    ..Two of the components of DRAF1 have now been identified as interferon regulatory factor 3 (IRF-3) and the transcriptional coactivator CREB-binding protein (CBP)/p300...
  89. pmc Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus
    Santhana G Devaraj
    Department of Microbiology and Immunology, Center of Biodefense and Emerging Infectious Diseases, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555 1019, USA
    J Biol Chem 282:32208-21. 2007
    ..Our data suggest that regulation of IRF-3-dependent innate antiviral defenses by PLpro may contribute to the establishment of SARS-CoV infection...
  90. pmc Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3
    Wenwen Zeng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Mol Cell 36:315-25. 2009
    ..Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation...
  91. pmc MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response
    Fajian Hou
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Cell 146:448-61. 2011
    ..These results suggest that a prion-like conformational switch of MAVS activates and propagates the antiviral signaling cascade...
  92. doi SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation
    Yong Ran
    College of Life Sciences, Wuhan University, China
    J Mol Cell Biol 3:283-92. 2011
    ....
  93. pmc TRIM11 negatively regulates IFNβ production and antiviral activity by targeting TBK1
    Younglang Lee
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
    PLoS ONE 8:e63255. 2013
    ..Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex...
  94. pmc Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes
    W C Au
    Oncology Center, Johns Hopkins University, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 92:11657-61. 1995
    ..Identification of this ISRE-binding protein may help us to understand the specificity in the various Stat pathways...
  95. pmc Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300
    M Yoneyama
    Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Japan
    EMBO J 17:1087-95. 1998
    ..These findings suggest that IRF-3 plays an important role in the virus-inducible primary activation of type I IFN and IFN-responsive genes...
  96. pmc Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation
    R Lin
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
    Mol Cell Biol 18:2986-96. 1998
    ....
  97. ncbi Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo
    M G Wathelet
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Mol Cell 1:507-18. 1998
    ..These observations provide a unique example of the coordinate activation of multiple transcriptional activator proteins and their highly cooperative assembly into a transcriptional enhancer complex in vivo...
  98. ncbi Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300
    W Suhara
    Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    J Biochem 128:301-7. 2000
    ..We previously reported that IRF-3 (interferon regulatory factor 3) is specifically phosphorylated on serine residues and directly transmits a virus-induced signal from ..
  99. ncbi Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3
    M J Servant
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, H3T 1E2 Canada
    J Biol Chem 276:355-63. 2001
    ..The failure of numerous well characterized pharmacological inhibitors to abrogate virus-induced IRF-3 phosphorylation suggests the involvement of a novel kinase activity in IRF-3 regulation by viruses...
  100. ncbi IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein
    E J Smith
    Department of Pathology and Kaplan Comprehensive Cancer Center, Molecular Oncology and Immunology Program, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 276:8951-7. 2001
    ....
  101. ncbi Control of IRF-3 activation by phosphorylation
    Mitsutoshi Yoneyama
    Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113 8613, Japan
    J Interferon Cytokine Res 22:73-6. 2002
    ....

Research Grants85

  1. A quantitative proteomics approach to understand viral immune evasion strategies
    Michele E Hardy; Fiscal Year: 2010
    ..Understanding these pathways and the mechanisms by which viruses evade the innate immune response may lead new approaches to attenuated vaccines or antiviral drug targets specifically designed to bypass viral evasion strategies. ..
  2. SUSAN ELAINE SWEENEY; Fiscal Year: 2015
    ..The transcription factors interferon regulatory factor 3 (IRF3) and IRF7 differentially regulate gene expression and feedback of type I IFN response...
  3. Michael David; Fiscal Year: 2014
    ..The proposed studies will extend our understanding of the contributions of IRFs and type I interferons in the development of Treg cells that are essential in the maintenance of self-tolerance. ..
  4. TLR4 Signaling in alcoholic liver disease
    Gyongyi Szabo; Fiscal Year: 2013
    ..Our results suggest that the absence of TLR4 but not of the MyD88 adaptor protects mice from alcoholic liver disease. ..
  5. Genhong Cheng; Fiscal Year: 2015
    ..We will also develop novel therapeutic agents to treat disease models associated with DNA virus infections such as genital herpes. ..
  6. Zhijian J Chen; Fiscal Year: 2015
    ..If successful, our research should significantly advance the fields of immunology and virology, and provide new approaches to harness the host innate immunity to combat viral and autoimmune diseases. ..
  7. ROBERT A LAFYATIS; Fiscal Year: 2015
    ....
  8. Role of IRF3 and RXRa Crosstalk in Host Response to Viral Infections
    Genhong Cheng; Fiscal Year: 2013
    ..Preliminary data in our lab has identified a novel Interferon Regulatory Factor 3(IRF3)-dependent but type I interferon independent pathway induced during innate immune response to ..
  9. Anti-interferon Activity of the Arenavirus Nucleoprotein
    Luis Martinez-Sobrido; Fiscal Year: 2012
    ..This knowledge should fuel the development of better antiviral strategies to combat human pathogenic arenaviruses. ..
  10. Martin E Dorf; Fiscal Year: 2015
    ..Insights from the proposed studies may ultimately facilitate design of therapies that may curtail IKK-related pathways in chronic inflammatory diseases or enhance TBK1 activity when needed to boost immunity. ..
  11. Mary P Stenzel-Poore; Fiscal Year: 2015
    ..Aim 2. To determine the mechanism by which the IFN fingerprint confers neuroprotection in response to ischemic injury. Aim 3. Test whether direct activation of IRF3/7 in the acute setting of stroke leads to ischemic neuroprotection. ..
  12. Mechanisms of Immunosuppressive Actions of Glucocorticoids
    Inez Rogatsky; Fiscal Year: 2011
    ..abstract_text> ..
  13. GEORGE ROBERT STARK; Fiscal Year: 2016
    ..abstract_text> ..
  14. The Role of Ubiquitination on TBK1 Function
    Roosevelt Boursiquot; Fiscal Year: 2010
    ..A greater understanding of TBK1-mediated antiviral defense may suggest potential therapeutic targets in clinical applications. ..
  15. Katherine A Fitzgerald; Fiscal Year: 2016
    ..signaling pathway involving Stimulator of IFN genes (STING), TANK binding kinase-1 (TBK-1) and interferon regulatory factor 3 (IRF3) to regulate transcription of type I IFN genes...
  16. Daisy Leung; Fiscal Year: 2016
    ..Through these studies, we expect to define the molecular basis for how RSV NS1/2 contributes to immune evasion and identify new targets for therapeutic and antiviral development. ..
  17. Stephen T Smale; Fiscal Year: 2015
    ....
  18. HARRY BERNARD GREENBERG; Fiscal Year: 2016
    ..It is our hypothesis that we can accomplish this aim by utilizing approaches recently validated for reovirus and orbiviruses. ..
  19. Interferon Regulatory Factors and Periodontal Disease
    Frank C Gibson; Fiscal Year: 2012
    ..The ultimate goal of this work is to begin to understand whether strategies to intercede in IRF3-signaling can be channeled to augment current PD treatment regimens. ..
  20. ERIK S FALCK-PEDERSEN; Fiscal Year: 2015
    ....
  21. Host defense against poxviruses and viral immune evasion
    Liang Deng; Fiscal Year: 2011
    ..abstract_text> ..
  22. YPE PETER DE JONG; Fiscal Year: 2015
    ..Results obtained by these experiments can help prioritize which immunomodulatory therapies should best be pursued into clinical development. ..
  23. MOLECULAR BIOLOGY AND PATHOGENESIS OF MOUSE ADENOVIRUS
    Katherine R Spindler; Fiscal Year: 2010
    ..A thorough knowledge of adenovirus basic biology is critical for the development of safe antiviral drugs, adenovirus-based gene transfer vectors, and vaccines. ..
  24. MAVS protein: A role of mitochondria in innate immunity and cardioprotection
    Kirk Peterson; Fiscal Year: 2013
    ..abstract_text> ..
  25. Jae U Jung; Fiscal Year: 2016
    ....
  26. Yuan Zhai; Fiscal Year: 2014
    ..This study dissects the immunological mechanism of liver IRI. Results will provide rationales for novel therapies to ameliorate liver IRI in clinics. ..
  27. Alan M Fogelman; Fiscal Year: 2016
    ..Project 6 will determine the mechanisms by which interferon regulatory factor 3 (IRF3) signaling regulates the function of the liver X receptor (LXR) and cholesterol metabolism in ..
  28. Modulation of Innate Immune Responses by Cytomegalovirus
    Klaus J Früh; Fiscal Year: 2012
    ..Ultimately, these in vitro results will allow us to test the importance of modulating the innate immune response in an emerging animal model for HCMV. ..
  29. Evaluating Innate Immune Responses in Dendritic Cells During HIV Infection
    JARROD SEAN JOHNSON; Fiscal Year: 2013
    ..Our laboratory has recently shown the existence of an interferon regulatory factor 3 (IRF3)-dependent innate response to HIV in DCs (24), but this response is cryptic since HIV does not ..
  30. Robert E Lanford; Fiscal Year: 2014
    ..In addition, persistent GBV-B infections would represent a new primate model for HCV disease progression. Furthermore, development of a primate model of targeted gene knockdown would be of great value in a number of research areas. ..
  31. Innate Immune Mechanism in Chlamydia Induced Acceleration of Atherosclerosis
    Moshe Arditi; Fiscal Year: 2013
    ..abstract_text> ..
  32. Regulation of Type I Interferon Gene Expression in the Innate Immune Response
    Katherine A Fitzgerald; Fiscal Year: 2010
    ..abstract_text> ..
  33. Activators and repressors of NFkappaB and IRF3/7 in innate immunity
    GEORGE ROBERT STARK; Fiscal Year: 2012
    ..Our findings have the potential to lead to new therapeutic approaches in several disease settings. ..
  34. AMER AZIZ BEG; Fiscal Year: 2014
    ..Aim 1: Generation, in vitro and in vivo characterization of AdV expressing distinct intracellular adjuvants. Aim 2: Defining the role of type 1 IFN in intracellular adjuvant-induced enhancement of AdV immune responses. ..
  35. FUNCTION OF IRF7 IN RESPONSE TO VIRUS INFECTION
    David Levy; Fiscal Year: 2004
    ..These studies should reveal important features of transcriptional regulatory mechanisms and uncover the nature of the antiviral alarm system. ..
  36. Signaling in Cells Chronically Exposed to Interferons
    Andrew Larner; Fiscal Year: 2009
    ..2) Determine the mechanisms by which Tc-PTP enhances dephosphorylation of Stat1 in previously desensitized cells. ..
  37. Listeria-induced cytosolic response and host immunity
    KRISTINA ANN ARCHER; Fiscal Year: 2010
    ..This work will contribute to the understanding of how inflammation generates long-term memory and may reveal new insights on methods to develop safe and effective vaccines. ..
  38. Novel Modifiers of Toll-like and RIG-like Receptor Signaling
    Saumendra N Sarkar; Fiscal Year: 2013
    ..Our long-term goal is to use these specific reagents to treat inflammatory and auto-immune diseases, which are caused by over or under-action of these receptors. ..
  39. A novel cytosolic immunosurveillance pathway
    RUSSELL E contact VANCE; Fiscal Year: 2010
    ..Adjuvants function by stimulating cells of the innate immune system. A better understanding of how adjuvants stimulate innate immunity will allow for the design of more effective and/or safer adjuvants. ..
  40. Viral Stress-inducible Gene Expression
    Ganes Sen; Fiscal Year: 2005
    ..These studies will illuminate the modes of cross-talk between the TLR and the Jak-STAT signaling pathways for appropriate gene induction in virus-infected cells. ..
  41. ROLE OF TOLL-LIKE RECEPTORS IN SKIN
    Robert Modlin; Fiscal Year: 2009
    ..abstract_text> ..
  42. Antiviral host responses by cytomegalovirus
    Klaus Frueh; Fiscal Year: 2005
    ..The major goals of this proposal include identification of 1) RhCMV gene(s) required for ISG downregulation and 2) host pathways targeted by the virus to accomplish this. ..
  43. HIV-1 Potently antagonizes innate cellular signaling pathways by targeting IRF3
    BRIAN PAUL DOEHLE; Fiscal Year: 2010
    ..preliminary studies have reveled antagonism of host defense pathways through a disruption of the host interferon regulatory factor 3 (IRF3) protein, one of the integral molecules for several innate immune defense pathways...
  44. Role of IRF3 and RXRa Crosstalk in Host Response to Viral Infections
    Genhong Cheng; Fiscal Year: 2008
    ..Preliminary data in our lab has identified a novel Interferon Regulatory Factor 3(IRF3)-dependent but type I interferon independent pathway induced during innate immune response to ..
  45. Hepatitis C Virus, Alcohol and Host Defense
    Gyongyi Szabo; Fiscal Year: 2007
    ..Results from these studies should reveal molecular and cellular mechanisms by which alcohol interacts with HCV infection to accelerate disease persistence and progression. [unreadable] [unreadable]..
  46. Molecular Mechanisms for IL-25-mediated Th2 Responses
    Xiaoxia Li; Fiscal Year: 2010
    ..With this improved understanding comes the potential to develop specific inhibitors of these pathways and perhaps novel therapeutics for the treatment of asthma. ..
  47. Mechanisms of Alcohol Mediated Organ and Tissue Damage
    Gyongyi Szabo; Fiscal Year: 2005
    ..3. Increase the involvement of young investigators in the study of alcohol research. 4. Provide an educational forum to participants. ..
  48. Molecular Mechanisms of IL-1R-TLR-Mediated Signaling
    Xiaoxia Li; Fiscal Year: 2008
    ..The long-term objective is to develop more effective anti-inflammatory and anti-atherogenic small molecule drugs. [unreadable] [unreadable] [unreadable]..
  49. Poxvirus regulation of NF-kB: Mechanisms for virulence
    Joanna Shisler; Fiscal Year: 2009
    ..Results obtained here may prove useful in devising novel strategies to overcome pathogenic effects of vaccinia, with implications for enhancing safety and efficacy of a smallpox vaccine. ..
  50. Act1 in CD40-/BAFFR-Mediated B Cell Survival
    Xiaoxia Li; Fiscal Year: 2009
    ..These findings will help us to elucidate the detailed regulatory mechanism for B cell homeostasis and opens new possibility to intervene the immune system. ..
  51. Ethanols role in mediation of monocyte suppression
    Gyongyi Szabo; Fiscal Year: 2009
    ..Investigation of the modulation of IL-10 and IL-12 by alcohol in dendritic cell function may identify biomarkers of alcohol-induced immune depression and reveal potential targets for therapy. ..
  52. SIGIRR A Negative Regulator of Toll-IL-IR Signaling
    Xiaoxia Li; Fiscal Year: 2009
    ..Specifically, the proposed studies should result in significant advances in the field of innate mucosal immunity and should also help us to determine the potential of SIGIRR as a target for developing anti-inflammatory drugs. ..
  53. Endothelial Toll-Like Receptor-4 Signaling in Sepsis
    John Harlan; Fiscal Year: 2008
    ..abstract_text> ..
  54. Does the HSV-1 latency associated transcript (LAT) encode a protein?
    Clinton Jones; Fiscal Year: 2008
    ..Studies will also determine whether LAT encoded proteins inhibit apoptosis, and whether these proteins are necessary for the latency reactivation cycle. [unreadable] [unreadable] [unreadable]..
  55. VLA-4 And VCAM-1 in Advanced Atherosclerosis
    John Harlan; Fiscal Year: 2005
    ..To complement the VLA- 4 studies, we will also examine the role of VCAM-1 in lesion initiation/progression in a model of conditional knockout of endothelial VCAM-1 (Aim 3). ..
  56. The A2a adenosine receptor modulates hyaluronan mediated lung inflammation
    MAUREEN RENEE HORTON; Fiscal Year: 2010
    ..We believe that these studies will provide the pre-clinical basis for the use of A2aR specific agonists in the treatment of inflammatory lung diseases such as idiopathic pulmonary fibrosis, chronic bronchitis and emphysema. ..
  57. INTRAPULMONARY ADHESION BLOCKADE IN ASTHMA
    John Harlan; Fiscal Year: 2002
    ..These studies address previously unexplored areas of integrin biology and pulmonary immune responses and have the potential to suggest new approaches to therapy in asthma. ..
  58. Death Receptors in Sepsis
    John Harlan; Fiscal Year: 2009
    ..This project will aid in our understanding of the cause of death and may suggest new therapies. ..
  59. Macrophage Apoptosis in Atherogenesis
    John Harlan; Fiscal Year: 2008
    ....
  60. Lassa and Nipah Virus Interferon-Antagonists
    CHRISTOPHER BASLER; Fiscal Year: 2003
    ..abstract_text> ..
  61. ROTAVIRUS VP5 PERMEABILIZES MEMBRANES
    ERICH MACKOW; Fiscal Year: 2002
    ..These studies address an essential step in the rotavirus entry process and basic mechanisms by which non-enveloped viral proteins permeabilize cellular membranes during entry. ..
  62. Influenza PDZ Ligand Directed Pathogenesis
    ERICH MACKOW; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  63. HANTAVIRUS CELL INTERACTIONS
    ERICH MACKOW; Fiscal Year: 2003
    ..Specific Aims: 1) beta3 Integrin Requirements for Hantavirus Infectivity; 2) Blocking beta3 Integrin-Hantavirus Interactions; 3) Transgenic Model of Hantavirus Infection and Pathogenesis. ..
  64. Intracellular Signaling Triggered by Tall-1/BCMA
    Hong Bing Shu; Fiscal Year: 2005
    ..The genes and their protein products identified in this study may be used as molecular targets for drug development against certain immune-deficient and autoimmune diseases. ..
  65. Racial Differences in IFN Transcriptional Response
    Daryl Lau; Fiscal Year: 2009
    ..between early virological responders and non-responders will lead to a better understanding of host pathways involved in the suppression of hepatitis C virus replication and the induction of a sustained virological response to therapy ..
  66. Therapeutic use of inhibitory DNA sequences in animal models of lupus
    Petar Lenert; Fiscal Year: 2006
    ..Future extension of these studies to humans may lead to the design of novel therapeutic agents for human SLE. [unreadable] [unreadable] [unreadable]..
  67. The cardiac interferon response to reovirus infection
    Barbara Sherry; Fiscal Year: 2008
    ..In sum, results will identify cell type-specific IFN-beta-related responses critical for protection against myocarditis, potentially providing new avenues for intervention against viral infections of the heart. ..
  68. Mechanism of Action of Inhibitory CpG Oligonucleotides
    Petar Lenert; Fiscal Year: 2009
    ..abstract_text> ..
  69. Mechanisms for Hormone-Dependent NF-kB Activation
    Allan Brasier; Fiscal Year: 2007
    ..These studies will identify new therapeutic targets that can disrupt the vicious cycle of inflammation and atherosclerosis. ..
  70. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  71. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  72. REGULATION OF CYTOKINE GENES IN MUCOSAL VIRAL INFECTION
    Allan Brasier; Fiscal Year: 2006
    ..Expression of dominant-negative NF-KB and CBP/p300 coactivators will be used to determine their effect on coactivator recruitment. These studies will identify signaling mechanisms and protein interactions in viral-induced inflammation. ..
  73. Poxvirus adverse effects on cardiac cells and the heart
    Barbara Sherry; Fiscal Year: 2005
    ..Studies proposed in this R21 application will provide the foundation for future in-depth studies with the goal of improving current and future smallpox vaccines. ..
  74. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  75. EBOLA VIRUS INTERFERON-ANTAGONISTS AND VIRULENCE
    CHRISTOPHER BASLER; Fiscal Year: 2003
    ..VP35 and VP24 may also prove to be attractive targets for new antiviral agents. Inhibition of anti-IFN factors may sensitize Ebola virus infected cells to the antiviral effects of IFN and may also enhance the effect of antiviral agents. ..
  76. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  77. ACUTE MYOCARDITIS--ROLES OF REOVIRUS AND INTERFERON BETA
    Barbara Sherry; Fiscal Year: 2001
    ..Reoviruses offer a unique tool to investigate the IFN response invoked by closely related viruses in the heart. Our work will be the first to identity cell factors that are determinants of this cardiac IFN response and myocarditis. ..