title: 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.affiliation: Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences (DIPAS), Lucknow Road, Timarpur, Delhi, 110054, India.
authors.forename: Drishya
authors.initials: D
authors.lastname: Diwaker
authors.forename: K P
authors.initials: KP
authors.lastname: Mishra
authors.forename: Lilly
authors.initials: L
authors.lastname: Ganju
authors.forename: S B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000276:immunology; D003715:Dengue / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D000072640:Interferon-Induced Helicase, IFIH1; D009000:Monocytes / Q000276:immunology / Q000821:virology; D010936:Plant Extracts / Q000494:pharmacology*; D011971:Receptors, Immunologic; D027343:Rhizome / Q000737:chemistry; D029771:Rhodiola / Q000737:chemistry*; D014452:Ubiquitins / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D010936:Plant Extracts; D011971:Receptors, Immunologic; D014452:Ubiquitins; C074034:ISG15 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1