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Virology. 2019 Sep 10;537:263-271. doi: 10.1016/j.virol.2019.09.004. [Epub ahead of print]
Role of TGF-β-activated kinase 1 (TAK1) activation in H5N1 influenza A virus-induced c-Jun terminal kinase activation and virus replication.
Sheng T1, Sun Y1, Sun J2, Prinz RA3, Peng D4, Liu X4, Xu X5.
Author information
1 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. 3 Department of Surgery, NorthShore University Health System, Evanston, IL, 60201, USA. 4 Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. 5 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Department of Cell and Molecular Medicine, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL60612, USA. Electronic address: xxl@yzu.edu.cn.
Abstract
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
Autophagy; Influenza A virus; JNK; NS1; TAK1; Virus replication
PMID: 31539775 DOI: 10.1016/j.virol.2019.09.004
Role of TGF-β-activated kinase 1 (TAK1) activation in H5N1 influenza A virus-induced c-Jun terminal kinase activation and virus replication.
Sheng T1, Sun Y1, Sun J2, Prinz RA3, Peng D4, Liu X4, Xu X5.
Author information
1 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. 3 Department of Surgery, NorthShore University Health System, Evanston, IL, 60201, USA. 4 Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China. 5 College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, PR China; Department of Cell and Molecular Medicine, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL60612, USA. Electronic address: xxl@yzu.edu.cn.
Abstract
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
Autophagy; Influenza A virus; JNK; NS1; TAK1; Virus replication
PMID: 31539775 DOI: 10.1016/j.virol.2019.09.004