NF-κB activation is a turn on for vaccinia virus phosphoprotein A49 to turn off NF-κB activation
Neidel S., Ren H., Torres AA., Smith GL.
Significance Vaccinia virus (VACV) encodes many proteins that inhibit innate immunity. For instance, protein A49 inhibits NF-κB activation by binding to β-TrCP. Here we show that A49 is phosphorylated on serine 7 and that this is necessary for binding β-TrCP and inhibition of NF-κB activation. Further, this phosphorylation occurs when the NF-κB pathway is stimulated and the kinase IKKβ is activated. Thus, A49 shows beautiful biological regulation, for activation of the pathway also activates the virus inhibitor of the pathway. The significance is seen in vivo, since VACVs expressing A49 S7A or S7E are less virulent than wild-type virus but more virulent than a virus lacking A49.