Nonstructural protein of infectious bursal disease virus inhibits apoptosis at the early stage of virus infection.
Infectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, carries a small nonstructural protein (NS). This protein has been implicated to play a role in the induction of apoptosis. In this study, we investigate the kinetics of viral replication during a single round of viral replication and examine the mechanism of IBDV-induced apoptosis. Our results show that it is caspase dependent and activates caspases 3 and 9. Nuclear factor kappa B (NF-kappaB) is also activated and is required for IBDV-induced apoptosis. The NF-kappaB inhibitor MG132 completely inhibited IBDV-induced DNA fragmentation, caspase 3 activation, and NF-kappaB activation. To study the function of the NS protein in this context, we generated the recombinant rGLS virus and an NS knockout mutant, rGLSNSdelta virus, using reverse genetics. Comparisons of the replication kinetics and markers for virally induced apoptosis indicated that the NS knockout mutant virus induces earlier and increased DNA fragmentation, caspase activity, and NF-kappaB activation. These results suggest that the NS protein has an antiapoptotic function at the early stage of virus infection.
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, MD 20742, USA.
Meihong
M
Liu
Vikram N
VN
Vakharia
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018175:Birnaviridae Infections / Q000473:pathology / Q000821:virology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D005819:Genetic Markers; D007243:Infectious bursal disease virus / Q000235:genetics / Q000472:pathogenicity*; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D009154:Mutation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011995:Recombination, Genetic; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D005819:Genetic Markers; D007976:Leupeptins; D016328:NF-kappa B; D017361:Viral Nonstructural Proteins; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde