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 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 marni shirt green 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 12n/1200 wella DUB targeting its K63-, K48- and K27-linked ubiquitin moieties.

BPLF1 also catalyzed removal of K63- and K48-linked ubiquitin 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.