Suppression of cGAS- and RIG-I-mediated innate immune signaling by Epstein-Barr virus deubiquitinase BPLF1.

Suppression of cGAS- and RIG-I-mediated innate immune signaling by Epstein-Barr virus deubiquitinase BPLF1.

Blog Article

Epstein-Barr virus (EBV) has developed effective strategies to evade host read more innate immune responses.Here we reported on mitigation of type I interferon (IFN) production by EBV deubiquitinase (DUB) BPLF1 through cGAS-STING and RIG-I-MAVS pathways.The two naturally occurring forms of BPLF1 exerted potent suppressive effect on cGAS-STING-, RIG-I- and TBK1-induced IFN production.

The observed suppression was reversed when DUB domain of BPLF1 was rendered catalytically inactive.The DUB activity of BPLF1 also facilitated EBV infection by counteracting cGAS-STING- and TBK1-mediated antiviral defense.BPLF1 associated with STING to act as an effective DUB targeting its K63-, K48- and K27-linked ubiquitin moieties.

BPLF1 also catalyzed removal of K63- and K48-linked ubiquitin motovox scooter parts chains on TBK1 kinase.The DUB activity of BPLF1 was required for its suppression of TBK1-induced IRF3 dimerization.Importantly, in cells stably carrying EBV genome that encodes a catalytically inactive BPLF1, the virus failed to suppress type I IFN production upon activation of cGAS and STING.

This study demonstrated IFN antagonism of BPLF1 mediated through DUB-dependent deubiquitination of STING and TBK1 leading to suppression of cGAS-STING and RIG-I-MAVS signaling.