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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
2019 ; 15
(10
): e1008062
Nephropedia Template TP
gab.com Text
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English Wikipedia
Induction of PGRN by influenza virus inhibits the antiviral immune responses
through downregulation of type I interferons signaling
#MMPMID31585000
Wei F
; Jiang Z
; Sun H
; Pu J
; Sun Y
; Wang M
; Tong Q
; Bi Y
; Ma X
; Gao GF
; Liu J
PLoS Pathog
2019[Oct]; 15
(10
): e1008062
PMID31585000
show ga
Type I interferons (IFNs) play a critical role in host defense against influenza
virus infection, and the mechanism of influenza virus to evade type I IFNs
responses remains to be fully understood. Here, we found that progranulin (PGRN)
was significantly increased both in vitro and in vivo during influenza virus
infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we
demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs
production by inhibiting the activation of NF-?B and IRF3 signaling. Furthermore,
we showed that PGRN directly interacted with NF-?B essential modulator (NEMO) via
its Grn CDE domains. We also verified that PGRN recruited A20 to deubiquitinate
K63-linked polyubiquitin chains on NEMO at K264. In addition, we found that
macrophage played a major source of PGRN during influenza virus infection, and
PGRN neutralizing antibodies could protect against influenza virus-induced
lethality in mice. Our data identify a PGRN-mediated IFN evasion pathway
exploited by influenza virus with implication in antiviral applications. These
findings also provide insights into the functions and crosstalk of PGRN in innate
immunity.