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

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A Correction to this article was published on 09 December 2021

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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.

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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

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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.

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Authors and Affiliations

  1. Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Lucknow Road, Timarpur, Delhi, 110054, India

    Navita Sharma, K. P. Mishra & Lilly Ganju

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  1. Navita Sharma
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  2. K. P. Mishra
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  3. Lilly Ganju
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Correspondence to K. P. Mishra.

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Sharma, N., Mishra, K.P. & Ganju, L. Salidroside exhibits anti-dengue virus activity by upregulating host innate immune factors. Arch Virol 161, 3331–3344 (2016). https://doi.org/10.1007/s00705-016-3034-1

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  • DOI: https://doi.org/10.1007/s00705-016-3034-1

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