VRK2 inhibits the replication of infectious bursal disease virus by phosphorylating RACK1 and suppressing apoptosis.

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by the infectious bursal disease virus (IBDV). Despite significant efforts, the lack of knowledge about host proteins that counteract IBDV replication has hindered progress in preventing and controlling IBD in chickens. This study identifies the mitochondria-associated protein vaccinia virus-related kinase 2 (VRK2) as an inhibitor of IBDV. Overexpression of VRK2 significantly reduced IBDV proliferation in DF-1 cells and chicken embryo fibroblasts (CEFs). Conversely, the absence of VRK2 resulted in higher viral loads in these cells. Additionally, we found that VRK2 interacts with voltage-dependent anion channel 2 (VDAC2) and Receptor for Activated C Kinase 1 (RACK1). Mechanistic studies revealed that VRK2 inhibits IBDV-induced apoptosis by targeting RACK1 phosphorylation, leading to reduced viral growth. This study enhances our understanding of VRK2's role in host anti-apoptotic mechanisms and offers novel insights into IBDV pathogenesis and vaccine development.