Inhibition of betanodavirus infection by inhibitors of endosomal acidification

Betanodaviruses, members of the family Nodaviridae, have small positive-stranded bipartite RNA genomes and are the causal agent of viral nervous necrosis (VNN) in many species of marine farmed fish. In the aquaculture industry, outbreaks of betanodavirus infection and spread in larval and juvenile f...

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Bibliographic Details
Published in:Archives of virology 2007-12, Vol.152 (12), p.2217-2224
Main Authors: Adachi, K, Ichinose, T, Takizawa, N, Watanabe, K, Kitazato, K, Kobayashi, N
Format: Article
Language:English
Subjects:
Ammonium Chloride - pharmacology
Animals
Antiviral Agents - pharmacology
Betanodavirus
Biological and medical sciences
Cells, Cultured
Chloroquine - pharmacology
Cytopathogenic Effect, Viral - drug effects
Drug dosages
Endocytosis - drug effects
Endosomes - drug effects
Endosomes - physiology
Endosomes - virology
Fundamental and applied biological sciences. Psychology
Hydrogen-Ion Concentration
Infections
Macrolides - pharmacology
Microbiology
Miscellaneous
Molecular biology
Monensin - pharmacology
Nodaviridae
Nodaviridae - drug effects
Nodaviridae - pathogenicity
Nodaviridae - physiology
Proteins
RNA polymerase
Viral infections
Virology
Viruses
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Summary:Betanodaviruses, members of the family Nodaviridae, have small positive-stranded bipartite RNA genomes and are the causal agent of viral nervous necrosis (VNN) in many species of marine farmed fish. In the aquaculture industry, outbreaks of betanodavirus infection and spread in larval and juvenile fish result in devastating damage and heavy economic loss. Although an urgent need exists to develop drugs that inhibit betanodavirus infection, there have been no reports about anti-betanodavirus drugs. Recently, it was reported that betanodaviruses were detected in the endosomes of infected cells, suggesting that betanodaviruses enter fish cells by endocytosis. This finding prompted us to examine whether blocking this endosomal pathway could provide a target for antiviral drug development. In this study, we examined the inhibitory effect of several lysosomotropic agents against betanodavirus infection in fish E-11 cells. The presence of 1 mM NH₄Cl or 1 μM chloroquine in the medium inhibited the entry of betanodaviruses into cells and inhibited viral infection. The lysosomotropic agents bafilomycin A1 and monensin also inhibited virus-induced cytopathology and virus production. Our data demonstrate that inhibitors of endosomal acidification are candidates as antiviral agents against betanodavirus.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-007-1061-7