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.

Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein

“…c-Jun N-terminal kinases (JNKs) are a family of protein kinases involved in regulating the host stress signaling pathway and reported to be implicated in host gene expression, cell death and senescence regulation (Yarza et al, 2016). JNK pathway activation and subsequently apoptosis induction are a hallmark of IAV infection and are factors essential for efficient IAV replication (Halder et al, 2011;Cannon et al, 2014;Nacken et al, 2014;Mehrbod et al, 2019;Zhang et al, 2019). Previous studies have reported the role of IAV NS1 in JNK stress signaling pathway activation (Nacken et al, 2014).…”

Inhibition of canine distemper virus replication by blocking pyrimidine nucleotide synthesis with A77 1726, the active metabolite of the anti-inflammatory drug leflunomide

“…Vero cells infected with CDV were incubated for 18 h in the absence or presence of the indicated inhibitors. Cell lysates were prepared and analysed for the levels of interested proteins or phosphorylation as reported previously [38]. The density of the bands was analysed by using NIH ImageJ software and normalized by the arbitrary units of their corresponding total proteins or β-actin.…”

Manipulation of Intestinal Antiviral Innate Immunity and Immune Evasion Strategies of Porcine Epidemic Diarrhea Virus

“…The virus-induced activation of JNK can regulate c-Jun and activator protein-1 (AP-1) transactivation function to promote the expression of proinflammatory cytokines. Similarly, multiple viruses exploit the JNK pathway to facilitate their replication or the success of viral protein expression [38]. p38 MAPK signal transduction is involved in the inflammatory response, immune response, and cell apoptosis [39].…”