Reduction of infectious bursal disease virus replication in cultured cells by proteasome inhibitors.
Infectious bursal disease virus (IBDV) is the etiological agent of a highly contagious disease in chickens. In a recent report, proteasome inhibitor MG132 has been shown to completely inhibit IBDV-induced apoptosis. This raises the possibility that the ubiquitin-proteasome pathway may be used by the virus to promote viral replication. In this study, we examined the interplay between IBDV replication and the ubiquitin-proteasome pathway in cultured cells. Treatment of DF-1 cells with the proteasome inhibitors MG132 or lactacystin significantly decreased virus release in the supernatant and prevented virus-induced cytopathic effect. Inhibition of the ubiquitin-proteasome pathway did reduce markedly viral RNA transcription and protein translation but not affect virus internalization. We also demonstrated that IBDV activates caspase pathway via triggering the efflux of cytochrome c in mitochondria into cytosol of infected cells. This activity was dose-dependently reduced by proteasome inhibitor treatment. Taken together, our data suggest that proteasome inhibitor reduces IBDV replication through inhibition of viral RNA transcription and protein synthesis, and thus preventing IBDV-induced apoptosis.
Institute of Animal Husbandry and Veterinary Medicine, Beijing Municipal Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Central Road, Haidian District, Beijing 100097, PR China. liujue@263.net
Jue
J
Liu
Li
L
Wei
Taozhen
T
Jiang
Lei
L
Shi
Jing
J
Wang
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D007243:Infectious bursal disease virus / Q000254:growth & development*; D007976:Leupeptins / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis; D053586:Virus Internalization / Q000187:drug effects
D000998:Antiviral Agents; D007976:Leupeptins; D061988:Proteasome Inhibitors; D012367:RNA, Viral; D014764:Viral Proteins; C067713:lactacystin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine