Kaposi’s sarcoma herpesvirus viral FLICE inhibitory protein modulates A20 deubiquitinase activity

KSHV viral FLICE inhibitory protein (vFLIP) is a potent activator of NF-κB signaling and an inhibitor of apoptosis and autophagy. Inhibition of vFLIP function and NF-κB signaling promotes lytic reactivation. Here we provide evidence for a novel function of vFLIP through inhibition of the deubiquitinating (DUB) activity of the negative regulator, A20. We demonstrate direct interaction of vFLIP with Itch and A20 and provide evidence for subsequent loss of A20 DUB activity. Our results provide further insight into the function of vFLIP in the regulation of NF-κB signaling.