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Archives of Virology

, Volume 161, Issue 12, pp 3331–3344 | Cite as

Salidroside exhibits anti-dengue virus activity by upregulating host innate immune factors

  • Navita Sharma
  • K. P. MishraEmail author
  • Lilly Ganju
Original article

Abstract

Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8+ T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.

Keywords

Antiviral Activity Vero Cell Dengue Virus Dengue Hemorrhagic Fever Salidroside 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

DENV

Dengue virus

IC50

Half-maximal inhibitory concentration

RIG-I

Retinoic acid inducible gene

IRF-3

Interferon regulatory factor 3

PKR

RNA-activated protein kinase

P-eIF2α

Phosphorylated eukaryotic initiation factor 2α

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

IFN-α

Interferon alpha

NK

Natural killer cells

DHF

Dengue hemorrhagic fever

DSS

Dengue shock syndrome

DC-SIGN

Dendritic cell-specific ICAM3-grabbing non-integrin

hPBMCs

human peripheral blood mononuclear cells

FBS

Fetal bovine serum: MOI: multiplicity of infection

MTT

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyltetrazoliumbromide

NO

Nitric oxide

TNF-α

Tumor necrosis factor alpha

Notes

Acknowledgments

The authors thank the Defense Research & Development Organization (DRDO), Ministry of Defence, Government of India, for financial support in the form of DIP-264. NS thanks the Council of Scientific and Industrial research for providing a fellowship in the form of a junior and senior research fellowship.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Immunomodulation LaboratoryDefence Institute of Physiology and Allied Sciences (DIPAS), DRDODelhiIndia

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