Cited by 225Mosquito-borne diseases and controlEndoplasmic Reticulum Stress and DiseaseViral Infectious Diseases and Gene Expression in Insects

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Antiviral Effects of an Iminosugar Derivative on Flavivirus Infections

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Wu, Shu-Fen, Lee, Chyan-Jang, Liao, Ching-Len, Dwek, Raymond A., Zitzmann, Nicole, Lin, Yi-Ling·2002·Journal of Virology

DOI 10.1128/jvi.76.8.3596-3604.2002PMC PMC136089

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Abstract

Endoplasmic reticulum (ER) alpha-glucosidase inhibitors, which block the trimming step of N-linked glycosylation, have been shown to eliminate the production of several ER-budding viruses. Here we investigated the effects of one such inhibitor, N-nonyl-deoxynojirimycin (NN-DNJ), a 9-carbon alkyl iminosugar derivative, on infection by Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2). In the presence of NN-DNJ, JEV and DEN-2 infections were suppressed in a dose-dependent manner. This inhibitory effect appeared to influence DEN-2 infection more than JEV infection, since lower concentrations of NN-DNJ substantially blocked DEN-2 replication. Secretion of the flaviviral glycoproteins E and NS1 was greatly reduced, and levels of DEN-2 viral RNA replication measured by fluorogenic reverse transcription-PCR were also decreased, by NN-DNJ. Notably, the viral glycoproteins, prM, E, and NS1 were found to associate transiently with the ER chaperone calnexin, and this interaction was affected by NN-DNJ, suggesting a potential role of calnexin in the folding of flaviviral glycoproteins. Additionally, in a mouse model of lethal challenge by JEV infection, oral delivery of NN-DNJ reduced the mortality rate. These findings show that NN-DNJ has an antiviral effect on flavivirus infection, likely through interference with virus replication at the posttranslational modification level, occurring mainly in the ER.

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Authors: Wu, S.-F., Lee, C.-J., Liao, C.-L., Dwek, R. A., Zitzmann, N., & Lin, Y.-L.
Affiliations: Institute of Biomedical Sciences, Academia Sinica (TW)
National Defense Medical Center (TW)
University of Oxford (GB)
Corresponding author: Lin, Yi-Ling
ORCID: Wu, Shu-Fen
Liao, Ching-Len
Dwek, Raymond A.
Zitzmann, Nicole
Lin, Yi-Ling
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2002-04-15
Volume: 76
Issue: 8
Pages: 3596-3604
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.76.8.3596-3604.2002
PMC: PMC136089
OpenAlex: W2159159412
Cited by: 220
References: 49
Citations by year: 2026: 5 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 14 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 7 · 2014: 10 · 2013: 13 · 2012: 10
FWCI: 6.97
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Keywords: iminosugars, flavivirus, Japanese encephalitis virus, dengue virus type 2, N-glycosylation, calnexin, glycoprotein folding, NS1 protein, PRM, viral RNA replication, antiviral agents, oral antiviral therapy
MeSH terms: Animals, Antiviral Agents, Cell Line, Dengue, Dengue Virus, Encephalitis Virus, Japanese, Encephalitis, Japanese, Female, Cricetinae, Mice, Inbred ICR, 1-Deoxynojirimycin, Mice, Glycoside Hydrolase Inhibitors

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Antiviral Effects of an Iminosugar Derivative on Flavivirus Infections

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