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

Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus. Antiviral Res. 2019 Jul 12;:104551 Authors: Miller JL, Hill ML, Brun J, Pountain A, Sayce AC, Zitzmann N 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 DENVand 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. Th...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research