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Alpha-mangostin inhibits dengue virus production and pro-inflammatory cytokine/chemokine expression in dendritic cells

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Abstract

Dengue virus (DENV) is transmitted to humans via the bite of an Aedes mosquito, causing dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. In the human skin, DENV first infects keratinocytes, dendritic cells, and macrophages. Monocytes that are recruited to the site of infection and differentiate into monocyte-derived dendritic cells (moDCs) are also infected by DENV. DENV-infected DCs secrete pro-inflammatory cytokines and chemokines to modulate the immune response. The viral load and massive pro-inflammatory cytokine/chemokine production, referred to as a ‘cytokine storm’, are associated with disease severity. We propose that an ideal drug for treatment of DENV infection should inhibit both virus production and the cytokine storm, and previously, we reported that alpha-mangostin (α-MG) inhibits both DENV replication and cytokine production in hepatocytes. However, the effect of α-MG on DENV-infected moDCs remains unknown. In this study, we investigated the effects of α-MG on DENV infection and pro-inflammatory cytokine/chemokine production in primary moDCs generated ex vivo from monocytes of healthy individuals. α-MG at the non-toxic concentrations of 20 and 25 μM reduced DENV production by more than 10-fold and 1,000-fold, respectively. Treatment with α-MG efficiently inhibited the infection of immature moDCs by all four serotypes of DENV. Time-of-addition studies suggested that α-MG (25 μM) inhibits DENV at the early stage of replication. In addition, α-MG markedly reduced cytokine/chemokine (TNF-α, CCL4, CCL5, CXCL10, IL6, IL1β, IL10, and IFN-α) transcription in DENV-infected immature moDCs. These findings suggest the potential of α-MG to be developed as a novel anti-DENV drug.

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Acknowledgements

This work was supported by grants from Mahidol University (R15610004) and the Thailand Research Fund (TRF IRG 5980006). MJ and PY were both supported by Chalermprakiat Grants from the Faculty of Medicine Siriraj Hospital, Mahidol University. AP was supported by the Research Center in Bioresources for Agriculture, Industry and Medicine, Chiang Mai University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Kevin Jones for critical reading and editing of the manuscript.

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Authors and Affiliations

  1. Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Petlada Yongpitakwattana, Atthapan Morchang, Nunghathai Sawasdee & Pa-thai Yenchitsomanus

  2. Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand

    Aussara Panya

  3. Research Center in Bioresources for Agriculture, Industry and Medicine, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand

    Aussara Panya

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  1. Petlada Yongpitakwattana
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  2. Atthapan Morchang
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  3. Aussara Panya
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  5. Pa-thai Yenchitsomanus
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Contributions

Petlada Yongpitakwattana, Atthapan Morchang, and Nunghathai Sawasdee: methodology, investigation, data curation, writing – original draft preparation. Aussara Panya: methodology, visualization, supervision, writing – reviewing and editing. Pa-thai Yenchitsomanus: conceptualization, project administration, funding acquisition, methodology, visualization, supervision, writing – reviewing and editing.

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Correspondence to Pa-thai Yenchitsomanus.

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All authors declare no personal or professional conflicts of interest, and no financial support from the companies that produce and/or distribute the drugs, devices, or materials described in this report.

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Yongpitakwattana, P., Morchang, A., Panya, A. et al. Alpha-mangostin inhibits dengue virus production and pro-inflammatory cytokine/chemokine expression in dendritic cells. Arch Virol 166, 1623–1632 (2021). https://doi.org/10.1007/s00705-021-05017-x

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  • DOI: https://doi.org/10.1007/s00705-021-05017-x

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