TY - JOUR
T1 - Rhodiola inhibits dengue virus multiplication by inducing innate immune response genes RIG-I, MDA5 and ISG in human monocytes
AU - Diwaker, Drishya
AU - Mishra, K. P.
AU - Ganju, Lilly
AU - Singh, S. B.
N1 - Funding Information:
This project was supported by The Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Ministry of Defence, Govt. of India, in the form of TASK-177. Drishya received financial support in the form of an INSPIRE fellowship from Department of Science and Technology, Govt. of India.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
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U2 - 10.1007/s00705-014-2028-0
DO - 10.1007/s00705-014-2028-0
M3 - Article
C2 - 24590566
AN - SCOPUS:84905221070
SN - 0304-8608
VL - 159
SP - 1975
EP - 1986
JO - Archives of Virology
JF - Archives of Virology
IS - 8
ER -