Role of TGF-β-activated kinase 1 (TAK1) activation in H5N1 influenza A virus-induced c-Jun terminal kinase activation and virus replication.
Adaptor Proteins, Signal Transducing
/ metabolism
Autophagy
HEK293 Cells
Host-Pathogen Interactions
Humans
Influenza A Virus, H5N1 Subtype
/ growth & development
MAP Kinase Kinase 4
/ metabolism
Mitogen-Activated Protein Kinases
/ metabolism
Plant Proteins
/ metabolism
Viral Nonstructural Proteins
/ metabolism
Virus Replication
Autophagy
Influenza A virus
JNK
NS1
TAK1
Virus replication
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
05
09
2019
accepted:
09
09
2019
pubmed:
21
9
2019
medline:
12
6
2020
entrez:
21
9
2019
Statut:
ppublish
Résumé
Activation of c-Jun terminal kinase (JNK) by the nonstructural protein 1 (NS1) of the H5N1 subtype of influenza A virus (IAV) plays an important role in inducing autophagy and virus replication. However, the mechanisms of NS1-induced JNK activation remain elusive. Here we first confirmed the ability of H5N1 (A/mallard/Huadong/S/2005) to activate JNK and to induce autophagy in 293T cells, a human embryonic kidney cell line. We further showed that TAK1, MAP kinase kinase 4 (MKK4), and JNK were activated in 293T cells transfected with the NS1 gene of the H5N1 virus. JNK activation by the NS1 protein or by H5N1 virus was blocked by 5Z-7-Oxozeaenol (5Z), a TAK1-specific inhibitor, and by TAK1 siRNA. Further study showed that 5Z and TAK1 siRNA suppressed H5N1 virus-induced autophagy and inhibited virus replication. Our study unveiled a previously unrecognized role of TAK1 in IAV replication, IAV-induced JNK activation, and autophagy.
Identifiants
pubmed: 31539775
pii: S0042-6822(19)30261-2
doi: 10.1016/j.virol.2019.09.004
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
INS1 protein, influenza virus
0
Plant Proteins
0
TAB3 protein, human
0
Viral Nonstructural Proteins
0
MMK4 protein, Medicago sativa
EC 2.7.11.24
Mitogen-Activated Protein Kinases
EC 2.7.11.24
MAP Kinase Kinase 4
EC 2.7.12.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
263-271Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.