Betanodavirus non-structural protein B2: A novel necrotic death factor that induces mitochondria-mediated cell death in fish cells
Abstract
The Betanodavirus non-structural protein B2 plays a role in silencing RNA interference (RNAi), which mediated regulation of animal and plant innate immune responses, but little is known regarding the role of B2 in cell death. The present study examined the effects of B2 on mitochondria-mediated necrotic cell death in grouper liver (GL-av) cells. B2 was expressed at 12 h post-infection (pi), with increased expression between 24 and 72 h pi by Western blot. B2 was transiently expressed to investigate possible novel protein functions. Transient expression of B2 in GL-av cells resulted in apoptotic cell features and positive TUNEL assays (28%) at 24 h post-transfection (pt). During mechanistic studies of cell death, B2 upregulated expression of the proapoptotic gene Bax (2.8 fold at 48 h pt) and induced loss of mitochondria membrane potential (MMP) but not mitochondrial cytochrome c release. Furthermore, over expression of Bcl-2 family member zfBcl-xL effectively prevented B2-induced, mitochondria-mediated necrotic cell death. Finally, using RNA interference to reduce B2 expression, both B2 and Bax expression were downregulated and RGNNV-infected cells were rescued from secondary necrosis. Taken together, our results suggest that B...Continue Reading
References
Citations
Related Concepts
Related Feeds
BCL-2 Family Proteins
BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis