Abstract | OBJECTIVES: METHODS: The viruses examined were a recently circulating seasonal influenza A(H3N2) virus strain A/Brisbane/10/2007, an older H3N2 strain A/Udorn/307/72, and A/Lviv/N6/2009, a strain representative of the currently circulating pandemic influenza A(H1N1)pdm09 virus. RESULTS: The inhibitors had the strongest effect on Brisbane/10 and NN-DNJ was more potent than NB-DNJ. Both compounds showed antiviral activity in cell culture against three human influenza A viruses in a strain-specific manner. Consistent with its action as an α- glucosidase inhibitor, NN-DNJ treatment resulted in an altered glycan processing of influenza haemagglutinin (HA) and neuraminidase (NA), confirmed by MS. NN-DNJ treatment was found to reduce the cell surface expression of the H3 subtype HA. The level of sialidase activity of NA was reduced in infected cells, but the addition of exogenous sialidase to the cells did not complement the NN-DNJ-mediated inhibition of virus replication. Using reassortant viruses, the drug susceptibility profile was determined to correlate with the origin of the HA. CONCLUSIONS:
NN-DNJ inhibits influenza A virus replication in a strain-specific manner that is dependent on the HA.
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Authors | S Hussain, J L Miller, D J Harvey, Y Gu, P B Rosenthal, N Zitzmann, J W McCauley |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 70
Issue 1
Pg. 136-52
(Jan 2015)
ISSN: 1460-2091 [Electronic] England |
PMID | 25223974
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. |
Chemical References |
- Antiviral Agents
- N-nonyl-1-deoxynojirimycin
- 1-Deoxynojirimycin
- miglustat
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Topics |
- 1-Deoxynojirimycin
(analogs & derivatives, pharmacology)
- Antiviral Agents
(pharmacology)
- Humans
- Influenza A Virus, H1N1 Subtype
(drug effects)
- Influenza A Virus, H3N2 Subtype
(drug effects, physiology)
- Microbial Sensitivity Tests
- Virus Replication
(drug effects)
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