Format

Send to

Choose Destination
Antiviral Res. 2019 Oct;170:104551. doi: 10.1016/j.antiviral.2019.104551. Epub 2019 Jul 12.

Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus.

Author information

1
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom. Electronic address: joanna.miller@bioch.ox.ac.uk.
2
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

Abstract

The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes. Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo. We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV. Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors. Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression. This effect required infectious DENV and was reversed by iminosugar treatment. Treatment also affected signalling of the IFNγ receptor and TNFα receptor. In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor. This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.

KEYWORDS:

Antiviral; Dengue virus; Iminosugar; Interferon gamma receptor; Macrophage; Mannose receptor; Receptor

PMID:
31306674
DOI:
10.1016/j.antiviral.2019.104551
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center