In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 2 ( 2023-2-21), p. e1011186-
Kurzfassung:
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 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 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.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011186
DOI:
10.1371/journal.ppat.1011186.g001
DOI:
10.1371/journal.ppat.1011186.g002
DOI:
10.1371/journal.ppat.1011186.g003
DOI:
10.1371/journal.ppat.1011186.g004
DOI:
10.1371/journal.ppat.1011186.g005
DOI:
10.1371/journal.ppat.1011186.g006
DOI:
10.1371/journal.ppat.1011186.g007
DOI:
10.1371/journal.ppat.1011186.g008
DOI:
10.1371/journal.ppat.1011186.g009
DOI:
10.1371/journal.ppat.1011186.g010
DOI:
10.1371/journal.ppat.1011186.s001
DOI:
10.1371/journal.ppat.1011186.s002
DOI:
10.1371/journal.ppat.1011186.s003
DOI:
10.1371/journal.ppat.1011186.s004
DOI:
10.1371/journal.ppat.1011186.s005
DOI:
10.1371/journal.ppat.1011186.s006
DOI:
10.1371/journal.ppat.1011186.r001
DOI:
10.1371/journal.ppat.1011186.r002
DOI:
10.1371/journal.ppat.1011186.r003
DOI:
10.1371/journal.ppat.1011186.r004
DOI:
10.1371/journal.ppat.1011186.r005
DOI:
10.1371/journal.ppat.1011186.r006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2205412-1
