Antiviral effects of deoxynojirimycin (DNJ)-based iminosugars in dengue virus-infected primary dendritic cells.

Abstract

Dendritic cells (DCs) are important targets for dengue virus (DENV) infection and play a significant role in the early immune response. Antiviral effects of iminosugars against DENV in primary cells have been demonstrated previously in monocyte-derived macrophages (MDMΦs). Given the important role played by DCs in innate immune defense against DENV, the antiviral effects of three deoxynojirimycin (DNJ) derivatives (NN-DNJ, EOO-DNJ and 2THO-DNJ) and a deoxygalactonojirimycin (DGJ) negative control were evaluated in DENV-infected primary human monocyte-derived immature DCs (imDCs). DNJ- but not DGJ-derivatives elicited antiviral activity in DENV-infected imDCs, similar to that observed in MDMΦs. The DNJ-derivatives inhibited DENV secretion in a dose-dependent manner. Endoplasmic reticulum (ER) α-glucosidase I inhibition by DNJ-derived iminosugars, at concentrations of 3.16 μM, correlated with a reduction in the specific infectivity of virions that were still secreted, as well as a reduction in DENV-induced tumour necrosis factor alpha secretion. This suggests iminosugar-mediated ER α-glucosidase I inhibition may give rise to further benefits during DENV infection, beyond the reduction in viral secretion associated with ER α-glucosidase II inhibition.

• Authors: Nilanka Perera, Juliane Brun, Dominic S Alonzi, Beatrice E Tyrrell, Joanna L Miller, Nicole Zitzmann
• Journal: Antiviral research (Antiviral Res) Vol. 199 Pg. 105269 (03 2022) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 35227758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• Antiviral Agents
• 1-Deoxynojirimycin

Topics

• 1-Deoxynojirimycin (pharmacology)
• Antiviral Agents (pharmacology, therapeutic use)
• Dendritic Cells
• Dengue (drug therapy)
• Dengue Virus
• Endoplasmic Reticulum
• Humans
• Macrophages