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Journal article
RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response
PloS one, v 7(10), pp e42583-e42583
03 Oct 2012
PMID: 23056170
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90-7501 ('2'-(4-Aminophenyl)-[2,5'-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-beta gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy.
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Details
- Title
- RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response
- Creators
- Fang Guo - Drexel UniversityJennifer Mead - Drexel UniversityNishat Aliya - Drexel UniversityLijuan Wang - Drexel UniversityAndrea Cuconati - Hepatitis B FoundationLai Wei - Peking UniversityKui Li - University of Tennessee Health Science CenterTimothy M. Block - Drexel UniversityJu-Tao Guo - Drexel UniversityJinhong Chang - Drexel University
- Publication Details
- PloS one, v 7(10), pp e42583-e42583
- Publisher
- Public Library Science
- Number of pages
- 9
- Grant note
- AI061441; AI069285 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA U01AI061441 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Hepatitis B Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000309454000002
- Scopus ID
- 2-s2.0-84867055703
- Other Identifier
- 991019168631604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology