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2016 ; 6
(ä): 32000
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Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which
enhances TNF-? production by mononuclear phagocytes
#MMPMID27561946
Cheng YL
; Lin YS
; Chen CL
; Tsai TT
; Tsai CC
; Wu YW
; Ou YD
; Chu YY
; Wang JM
; Yu CY
; Lin CF
Sci Rep
2016[Aug]; 6
(ä): 32000
PMID27561946
show ga
Infection by the dengue virus (DENV) threatens global public health due to its
high prevalence and the lack of effective treatments. Host factors may contribute
to the pathogenesis of DENV; herein, we investigated the role of nuclear factor
(erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear
phagocytes. DENV infection selectively activates Nrf2 following nuclear
translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like
ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type
lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression.
Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3
(TLR3)-independent tumor necrosis factor (TNF)-? production following DENV
infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear
translocation/activation and CLEC5A expression which increases DENV-induced TNF-?
production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-? in brains of
DENV-infected mice. These results demonstrate that DENV infection causes
Nrf2-regulated TNF-? production by increasing levels of CLEC5A.