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.