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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+Pathog
2018 ; 14
(5
): e1007067
Nephropedia Template TP
gab.com Text
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Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by
promoting degradation of the MAVS/TRAF3/TRAF6 signalosome
#MMPMID29734366
Zhang L
; Liu J
; Qian L
; Feng Q
; Wang X
; Yuan Y
; Zuo Y
; Cheng Q
; Miao Y
; Guo T
; Zheng X
; Zheng H
PLoS Pathog
2018[May]; 14
(5
): e1007067
PMID29734366
show ga
During RNA virus infection, the adaptor protein MAVS recruits TRAF3 and TRAF6 to
form a signalosome, which is critical to induce the production of type I
interferons (IFNs) and proinflammatory cytokines. While activation of the
MAVS/TRAF3/TRAF6 signalosome is well studied, the negative regulation of the
signalosome remains largely unknown. Here we report that RNA viruses specifically
promote the deubiquitinase OTUD1 expression by NF-?B-dependent mechanisms at the
early stage of viral infection. Furthermore, OTUD1 upregulates protein levels of
intracellular Smurf1 by removing Smurf1 ubiquitination. Importantly, RNA virus
infection promotes the binding of Smurf1 to MAVS, TRAF3 and TRAF6, which leads to
ubiquitination-dependent degradation of every component of the MAVS/TRAF3/TRAF6
signalosome and subsequent potent inhibition of IFNs production. Consistently,
OTUD1-deficient mice produce more antiviral cytokines and are more resistant to
RNA virus infection. Our findings reveal a novel immune evasion mechanism
exploited by RNA viruses, and elucidate a negative feedback loop of
MAVS/TRAF3/TRAF6 signaling mediated by the OTUD1-Smurf1 axis during RNA virus
infection.
|Adaptor Proteins, Signal Transducing/*metabolism
[MESH]
|Animals
[MESH]
|Gene Knockdown Techniques
[MESH]
|HEK293 Cells
[MESH]
|Humans
[MESH]
|Immunity, Innate/*immunology
[MESH]
|Interferon Type I/genetics/metabolism
[MESH]
|Interferon-beta/genetics/metabolism
[MESH]
|Mice
[MESH]
|RNA Virus Infections/immunology/prevention & control
[MESH]