Role of c-Jun terminal kinase (JNK) activation in influenza A virus-induced autophagy and replication

Jingting Zhang; Tao Ruan; Tianyu Sheng; Jiongjiong Wang; Jing Sun; Jin Wang; Richard A. Prinz; Daxin Peng; Xiufan Liu; Xiulong Xu

doi:10.1016/j.virol.2018.09.020

Role of c-Jun terminal kinase (JNK) activation in influenza A virus-induced autophagy and replication

Jingting Zhang, Tao Ruan, Tianyu Sheng, Jiongjiong Wang, Jing Sun, Jin Wang, Richard A. Prinz, Daxin Peng, Xiufan Liu, Xiulong Xu

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

The non-structural protein 1 (NS1) of different influenza A virus (IAV) strains can differentially regulate the activity of c-Jun terminal kinase (JNK) and PI-3 kinase (PI3K). Whether varying JNK and PI3K activation impacts autophagy and IAV replication differently remains uncertain. Here we report that H5N1 (A/mallard/Huadong/S/2005) influenza A virus induced functional autophagy, as evidenced by increased LC3 lipidation and decreased p62 levels, and the presence of autolysosomes in chicken fibroblast cells. H9N2 (A/chicken/Shanghai/F/98) virus weakly induced autophagy, whereas H1N1 virus (A/PR/8/34, PR8) blocked autophagic flux. H5N1 virus activated JNK but inhibited the PI-3 kinase pathway. In contrast, N9N2 virus infection led to modest JNK activation and strong PI-3 kinase activation; whereas H1N1 virus activated the PI-3 kinase pathway but did not activate JNK. SP600125, a JNK inhibitor, inhibited H5N1 virus-induced autophagy and virus replication in a DF-1 chicken fibroblast cell line. Our study uncovered a previously unrecognized role of JNK in IAV replication and autophagy.

Original language	English (US)
Pages (from-to)	1-12
Number of pages	12
Journal	Virology
Volume	526
DOIs	https://doi.org/10.1016/j.virol.2018.09.020
State	Published - Jan 2 2019

Keywords

Autophagy
Influenza A virus
JNK
NS1
PI-3 kinase

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2018.09.020

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title = "Role of c-Jun terminal kinase (JNK) activation in influenza A virus-induced autophagy and replication",

abstract = "The non-structural protein 1 (NS1) of different influenza A virus (IAV) strains can differentially regulate the activity of c-Jun terminal kinase (JNK) and PI-3 kinase (PI3K). Whether varying JNK and PI3K activation impacts autophagy and IAV replication differently remains uncertain. Here we report that H5N1 (A/mallard/Huadong/S/2005) influenza A virus induced functional autophagy, as evidenced by increased LC3 lipidation and decreased p62 levels, and the presence of autolysosomes in chicken fibroblast cells. H9N2 (A/chicken/Shanghai/F/98) virus weakly induced autophagy, whereas H1N1 virus (A/PR/8/34, PR8) blocked autophagic flux. H5N1 virus activated JNK but inhibited the PI-3 kinase pathway. In contrast, N9N2 virus infection led to modest JNK activation and strong PI-3 kinase activation; whereas H1N1 virus activated the PI-3 kinase pathway but did not activate JNK. SP600125, a JNK inhibitor, inhibited H5N1 virus-induced autophagy and virus replication in a DF-1 chicken fibroblast cell line. Our study uncovered a previously unrecognized role of JNK in IAV replication and autophagy.",

keywords = "Autophagy, Influenza A virus, JNK, NS1, PI-3 kinase",

author = "Jingting Zhang and Tao Ruan and Tianyu Sheng and Jiongjiong Wang and Jing Sun and Jin Wang and Prinz, {Richard A.} and Daxin Peng and Xiufan Liu and Xiulong Xu",

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AU - Zhang, Jingting

AU - Ruan, Tao

AU - Sheng, Tianyu

AU - Wang, Jiongjiong

AU - Sun, Jing

AU - Wang, Jin

AU - Prinz, Richard A.

AU - Peng, Daxin

AU - Liu, Xiufan

AU - Xu, Xiulong

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N2 - The non-structural protein 1 (NS1) of different influenza A virus (IAV) strains can differentially regulate the activity of c-Jun terminal kinase (JNK) and PI-3 kinase (PI3K). Whether varying JNK and PI3K activation impacts autophagy and IAV replication differently remains uncertain. Here we report that H5N1 (A/mallard/Huadong/S/2005) influenza A virus induced functional autophagy, as evidenced by increased LC3 lipidation and decreased p62 levels, and the presence of autolysosomes in chicken fibroblast cells. H9N2 (A/chicken/Shanghai/F/98) virus weakly induced autophagy, whereas H1N1 virus (A/PR/8/34, PR8) blocked autophagic flux. H5N1 virus activated JNK but inhibited the PI-3 kinase pathway. In contrast, N9N2 virus infection led to modest JNK activation and strong PI-3 kinase activation; whereas H1N1 virus activated the PI-3 kinase pathway but did not activate JNK. SP600125, a JNK inhibitor, inhibited H5N1 virus-induced autophagy and virus replication in a DF-1 chicken fibroblast cell line. Our study uncovered a previously unrecognized role of JNK in IAV replication and autophagy.

AB - The non-structural protein 1 (NS1) of different influenza A virus (IAV) strains can differentially regulate the activity of c-Jun terminal kinase (JNK) and PI-3 kinase (PI3K). Whether varying JNK and PI3K activation impacts autophagy and IAV replication differently remains uncertain. Here we report that H5N1 (A/mallard/Huadong/S/2005) influenza A virus induced functional autophagy, as evidenced by increased LC3 lipidation and decreased p62 levels, and the presence of autolysosomes in chicken fibroblast cells. H9N2 (A/chicken/Shanghai/F/98) virus weakly induced autophagy, whereas H1N1 virus (A/PR/8/34, PR8) blocked autophagic flux. H5N1 virus activated JNK but inhibited the PI-3 kinase pathway. In contrast, N9N2 virus infection led to modest JNK activation and strong PI-3 kinase activation; whereas H1N1 virus activated the PI-3 kinase pathway but did not activate JNK. SP600125, a JNK inhibitor, inhibited H5N1 virus-induced autophagy and virus replication in a DF-1 chicken fibroblast cell line. Our study uncovered a previously unrecognized role of JNK in IAV replication and autophagy.

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Role of c-Jun terminal kinase (JNK) activation in influenza A virus-induced autophagy and replication

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Keywords

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