RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response

Fang Guo, Jennifer Mead, Nishat Aliya, Lijuan Wang, Andrea Cuconati, Lai Wei, Kui Li, Timothy M. Block, Ju Tao Guo, Jinhong Chang

Research output: Contribution to journalArticle

12 Citations (Scopus)

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-β 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.

Original languageEnglish (US)
Article numbere42583
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 3 2012

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Pattern Recognition Receptors
agonists
Antiviral Agents
Viruses
Signal transduction
receptors
Virus Diseases
Signal Transduction
interferons
Cytokines
viruses
Interferon Type I
signal transduction
Toll-Like Receptors
Blood vessels
p38 Mitogen-Activated Protein Kinases
cytokines
inflammation
Innate Immunity
Gene expression

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Guo, F., Mead, J., Aliya, N., Wang, L., Cuconati, A., Wei, L., ... Chang, J. (2012). RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response. PloS one, 7(10), [e42583]. https://doi.org/10.1371/journal.pone.0042583

RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response. / Guo, Fang; Mead, Jennifer; Aliya, Nishat; Wang, Lijuan; Cuconati, Andrea; Wei, Lai; Li, Kui; Block, Timothy M.; Guo, Ju Tao; Chang, Jinhong.

In: PloS one, Vol. 7, No. 10, e42583, 03.10.2012.

Research output: Contribution to journalArticle

Guo, F, Mead, J, Aliya, N, Wang, L, Cuconati, A, Wei, L, Li, K, Block, TM, Guo, JT & Chang, J 2012, 'RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response', PloS one, vol. 7, no. 10, e42583. https://doi.org/10.1371/journal.pone.0042583
Guo F, Mead J, Aliya N, Wang L, Cuconati A, Wei L et al. RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response. PloS one. 2012 Oct 3;7(10). e42583. https://doi.org/10.1371/journal.pone.0042583
Guo, Fang ; Mead, Jennifer ; Aliya, Nishat ; Wang, Lijuan ; Cuconati, Andrea ; Wei, Lai ; Li, Kui ; Block, Timothy M. ; Guo, Ju Tao ; Chang, Jinhong. / RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response. In: PloS one. 2012 ; Vol. 7, No. 10.
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