The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Antiviral Effects of an Iminosugar Derivative on Flavivirus Infections
Open accessAbstract
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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Metadata
- 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
- Publisher
- American Society for Microbiology
- Published
- 2002-04-15
- Volume
- 76
- Issue
- 8
- Pages
- 3596-3604
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- 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
- 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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