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

Journal article

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: Perera, N; Brun, J; Alonzi, DS; Tyrrell, BE; Miller, JL

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Antiviral Research
• Volume: 199
• Article number: 105269
• Publication date: 2022-02-25
• DOI: 10.1016/j.antiviral.2022.105269
• ISSN: 0166-3542
• Language: English
• Keywords: FFR