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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 J+Virol
2019 ; 93
(7
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Epigenetic Modification Is Regulated by the Interaction of Influenza A Virus
Nonstructural Protein 1 with the De Novo DNA Methyltransferase DNMT3B and
Subsequent Transport to the Cytoplasm for K48-Linked Polyubiquitination
#MMPMID30651365
Liu S
; Liu L
; Xu G
; Cao Z
; Wang Q
; Li S
; Peng N
; Yin J
; Yu H
; Li M
; Xia Z
; Zhou L
; Lin Y
; Wang X
; Li Q
; Zhu C
; Yang X
; Wang J
; She Y
; Lu M
; Zhu Y
J Virol
2019[Apr]; 93
(7
): ä PMID30651365
show ga
The influenza virus nonstructural protein 1 (NS1) is a nonstructural protein that
plays a major role in antagonizing host interferon responses during infection.
However, a clear role for the NS1 protein in epigenetic modification has not been
established. In this study, NS1 was found to regulate the expression of some key
regulators of JAK-STAT signaling by inhibiting the DNA methylation of their
promoters. Furthermore, DNA methyltransferase 3B (DNMT3B) is responsible for this
process. Upon investigating the mechanisms underlying this event, NS1 was found
to interact with DNMT3B but not DNMT3A, leading to the dissociation of DNMT3B
from the promoters of the corresponding genes. In addition, the interaction
between NS1 and DNMT3B changed the localization of DNMT3B from the nucleus to the
cytosol, resulting in K48-linked ubiquitination and degradation of DNMT3B in the
cytosol. We conclude that NS1 interacts with DNMT3B and changes its localization
to mediate K48-linked polyubiquitination, subsequently contributing to the
modulation of the expression of JAK-STAT signaling suppressors.IMPORTANCE The
nonstructural protein 1 (NS1) of the influenza A virus (IAV) is a multifunctional
protein that counters cellular antiviral activities and is a virulence factor.
However, the involvement of NS1 in DNA methylation during IAV infection has not
been established. Here, we reveal that the NS1 protein binds the cellular DNMT3B
DNA methyltransferase, thereby inhibiting the methylation of the promoters of
genes encoding suppressors of JAK-STAT signaling. As a result, these suppressor
genes are induced, and JAK-STAT signaling is inhibited. Furthermore, we
demonstrate that the NS1 protein transports DNMT3B to the cytoplasm for
ubiquitination and degradation. Thus, we identify the NS1 protein as a potential
trigger of the epigenetic deregulation of JAK-STAT signaling suppressors and
illustrate a novel mechanism underlying the regulation of host immunity during
IAV infection.