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

tetano

Editor, Senior Moderator
Virology. 2018 Oct 10;526:1-12. doi: 10.1016/j.virol.2018.09.020. [Epub ahead of print]
[h=1]Role of c-Jun terminal kinase (JNK) activation in influenza A virus-induced autophagy and replication.[/h] Zhang J[SUP]1[/SUP], Ruan T[SUP]1[/SUP], Sheng T[SUP]1[/SUP], Wang J[SUP]1[/SUP], Sun J[SUP]2[/SUP], Wang J[SUP]3[/SUP], Prinz RA[SUP]4[/SUP], Peng D[SUP]5[/SUP], Liu X[SUP]5[/SUP], Xu X[SUP]6[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.


[h=4]KEYWORDS:[/h] Autophagy; Influenza A virus; JNK; NS1; PI-3 kinase

PMID: 30316042 DOI: 10.1016/j.virol.2018.09.020
 
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