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

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

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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  1. [35]Monath, T. P., and F. X. Heinz. 1996. Flaviviruses, p. 961-1034. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), Fields virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, Pa.
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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
Venue
Journal of Virology
Published
2002-04-15
Volume
76
Issue
8
Pages
3596-3604
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
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
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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