Nonstructural Protein of Infectious Bursal Disease Virus Inhibits Apoptosis at the Early Stage of Virus Infection

Abstract

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.

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

“…These observations clearly show that RACK1 is involved in the regulation of apoptosis. In addition, it has been reported that the NF-B transcription factor promotes the expression of RACK1 and that RACK1 acts downstream of NF-B in facilitating cell survival (30), whereas NF-B could be activated during IBDV infection (23). Therefore, it is very likely that NF-B is involved in the RACK1 inhibition of IBDV-induced apoptosis in DF-1 cell lines.…”

“…VP5 inhibited apoptosis early during infection (23,24) but induced apoptosis at a later stage of infection (25), suggesting that VP5 may play different roles at different stages of IBDV infection. Our previous report indicated that VP5 induced apoptosis and that this induction resulted from interaction with VDAC2 in the mitochondrion of host cells (25).…”

“…The nonstructural viral protein VP5 only exists in IBDV-infected cells and plays different roles in IBDV-induced apoptosis during IBDV infection. VP5 inhibits apoptosis early during infection (23,24), whereas it induces apoptosis at a later stage of infection (4,25,26).…”

Identification and Functional Analysis of the Novel ORF4 Protein Encoded by Porcine Circovirus Type 2

“…Infected host cells undergo apoptosis to limit viral propagation (25). Therefore, many viruses carry antiapoptotic factors to facilitate replication, such as poliovirus (29), rotavirus (30), influenza virus (31,32), dengue virus (33), infectious bursal disease virus (34), and cowpox virus (35). To determine , 25 m).…”

Protein X of Borna Disease Virus Inhibits Apoptosis and Promotes Viral Persistence in the Central Nervous Systems of Newborn-Infected Rats

“…The Bcl-2 homologues encoded by lymphotropic gammaherpesviruses (19,20,31), the E1B-19K protein of adenovirus (36,49), vMIA of human cytomegalovirus (2), and the M11L protein of myxoma virus (12), among many others, are able to abrogate the activity of proapoptotic Bcl-2 members that act on mitochondria. RNA viruses from different families are similarly able to interfere with apoptosis at different stages of the process (9,29,30,43). However, all mitochondrion-localized proteins of RNA viruses identified thus far stimulate rather than inhibit apoptosis.…”