PMID- 35227758 OWN - NLM STAT- MEDLINE DCOM- 20220502 LR - 20221221 IS - 1872-9096 (Electronic) IS - 0166-3542 (Print) IS - 0166-3542 (Linking) VI - 199 DP - 2022 Mar TI - Antiviral effects of deoxynojirimycin (DNJ)-based iminosugars in dengue virus-infected primary dendritic cells. PG - 105269 LID - S0166-3542(22)00037-7 [pii] LID - 10.1016/j.antiviral.2022.105269 [doi] LID - 105269 AB - 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 (MDMPhis). 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 MDMPhis. The DNJ-derivatives inhibited DENV secretion in a dose-dependent manner. Endoplasmic reticulum (ER) alpha-glucosidase I inhibition by DNJ-derived iminosugars, at concentrations of 3.16 muM, 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 alpha-glucosidase I inhibition may give rise to further benefits during DENV infection, beyond the reduction in viral secretion associated with ER alpha-glucosidase II inhibition. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Perera, Nilanka AU - Perera N AD - Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK; Department of Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka. Electronic address: nilanka@sjp.ac.lk. FAU - Brun, Juliane AU - Brun J AD - Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: juliane.brun@path.ox.ac.uk. FAU - Alonzi, Dominic S AU - Alonzi DS AD - Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: dominic.alonzi@ctl.ox.ac.uk. FAU - Tyrrell, Beatrice E AU - Tyrrell BE AD - Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: beatrice.tyrrell@gmail.com. FAU - Miller, Joanna L AU - Miller JL AD - Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: joanna.miller@medsci.ox.ac.uk. FAU - Zitzmann, Nicole AU - Zitzmann N AD - Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: Nicole.zitzmann@bioch.ox.ac.uk. LA - eng GR - 203853/Z/16/Z/WT_/Wellcome Trust/United Kingdom GR - 105402/Z/14/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220225 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antiviral Agents) RN - 19130-96-2 (1-Deoxynojirimycin) SB - IM MH - 1-Deoxynojirimycin/pharmacology MH - Antiviral Agents/pharmacology/therapeutic use MH - Dendritic Cells MH - *Dengue/drug therapy MH - *Dengue Virus MH - Endoplasmic Reticulum MH - Humans MH - Macrophages PMC - PMC9760573 OTO - NOTNLM OT - Antiviral effects OT - Dendritic cells OT - Dengue OT - Iminosugars OT - alpha-glucosidases COIS- Authors NP, JB, DA, BET, JLM and NZ declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/03/02 06:00 MHDA- 2022/05/03 06:00 PMCR- 2022/03/01 CRDT- 2022/03/01 05:47 PHST- 2021/12/05 00:00 [received] PHST- 2022/02/12 00:00 [revised] PHST- 2022/02/22 00:00 [accepted] PHST- 2022/03/02 06:00 [pubmed] PHST- 2022/05/03 06:00 [medline] PHST- 2022/03/01 05:47 [entrez] PHST- 2022/03/01 00:00 [pmc-release] AID - S0166-3542(22)00037-7 [pii] AID - 105269 [pii] AID - 10.1016/j.antiviral.2022.105269 [doi] PST - ppublish SO - Antiviral Res. 2022 Mar;199:105269. doi: 10.1016/j.antiviral.2022.105269. Epub 2022 Feb 25.