Fig 9.

A schematic model demonstrating the inhibition of NF-κB signaling by BPLF1 in the EBV life cycle. In EBV latent infection, NF-κB is activated by viral LMP1 protein; TRAF6 associates with LMP1 and is constitutively polyubiquitinated. Activation of NF-κB confers cell survival (83) and inhibition of spontaneous lytic replication as well (24). Changes in the host cell microenvironment or other unknown triggers can downregulate the NF-κB activity and disrupt the balance between the latent cycle and the lytic cycle of EBV (61). Once lytic replication is induced, BPLF1 then deubiquitinates and inactivates TRAF6 to further block NF-κB signaling, promoting efficient viral genome replication.