Rhodiola inhibits dengue virus multiplication by inducing innate immune response genes RIG-I, MDA5 and ISG in human monocytes.

Abstract

Recognition of virus infection by retinoic acid-inducible gene (RIG) I and melanoma differentiation-associated protein (MDA) 5, which are RNA helicases, and interferon-stimulated gene (ISG) 15 activates cascades of signal transduction pathways leading to production of type I interferons and proinflammatory cytokines that orchestrate the elimination of the viruses. However, it has been demonstrated that RNA-helicase-mediated innate immunity plays an essential role in defending the host from infection. In our efforts to identify plant-derived antivirals that selectively enhance ISG- and RNA-helicase-mediated antiviral immune responses, we identified a plant, rhodiola, that significantly promoted ISG, RIG-I and MDA 5 gene expression and an antiviral immune response against dengue virus (DENV) infection. Rhodiola induced interferon (IFN) β and other cytokines, including IL-1β, TNF-α, IL-6 and IL-8, in infected cells. It was also found that rhodiola upregulated phosphorylated eIF-2α, PKR and NF-kB in infected cells. In addition, the number of NK cells was also increased by rhodiola treatment in dengue-virus-infected human PBMCs. Treatment with a crude extract of rhodiola (RAE) resulted in effects in the 20 % range, which is similar to the magnitude of the same effects observed in DENV infections. Taken together, our results imply that rhodiola induces pharmacological modulation of RIG-I, MDA 5 and ISG signal transduction pathways in favor of the induction of a beneficial antiviral immune response against dengue virus, which can be a novel therapeutic strategy for management of infection.

• Authors: Drishya Diwaker, K P Mishra, Lilly Ganju, S B Singh
• Journal: Archives of virology (Arch Virol) Vol. 159 Issue 8 Pg. 1975-86 (Aug 2014) ISSN: 1432-8798 [Electronic] Austria
• PMID: 24590566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Cytokines
• Plant Extracts
• Receptors, Immunologic
• Ubiquitins
• ISG15 protein, human
• DDX58 protein, human
• IFIH1 protein, human
• DEAD Box Protein 58
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1

Topics

• Antiviral Agents (pharmacology)
• Cytokines (genetics, immunology)
• DEAD Box Protein 58
• DEAD-box RNA Helicases (genetics, immunology)
• Dengue (drug therapy, genetics, immunology, virology)
• Dengue Virus (drug effects, physiology)
• Humans
• Immunity, Innate (drug effects)
• Interferon-Induced Helicase, IFIH1
• Monocytes (immunology, virology)
• Plant Extracts (pharmacology)
• Receptors, Immunologic
• Rhizome (chemistry)
• Rhodiola (chemistry)
• Ubiquitins (genetics, immunology)
• Up-Regulation (drug effects)
• Virus Replication (drug effects)