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Journal of Virology, April 2006, p. 3369-3377, Vol. 80, No. 7
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.7.3369-3377.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland 20742
Received 2 September 2005/ Accepted 3 January 2006
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-
B) is also activated and is required for IBDV-induced apoptosis. The NF-
B inhibitor MG132 completely inhibited IBDV-induced DNA fragmentation, caspase 3 activation, and NF-
B activation. To study the function of the NS protein in this context, we generated the recombinant rGLS virus and an NS knockout mutant, rGLSNS
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-
B activation. These results suggest that the NS protein has an antiapoptotic function at the early stage of virus infection.
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