tetano
Editor, Senior Moderator
Cell Microbiol. 2017 Jan 11. doi: 10.1111/cmi.12721. [Epub ahead of print]
[h=1]Influenza A virus NS1 protein-induced JNK activation and apoptosis are not functionally linked.[/h] Nacken W[SUP]1[/SUP], Wixler V[SUP]1[/SUP], Ehrhardt C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Ludwig S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Expression of the influenza A virus (IAV) non-structural protein NS1 results in the activation of c-Jun N-terminal kinase (JNK). Both NS1 and JNK are involved in apoptosis induction. To investigate their interrelationship, we stably expressed a tamoxifen inducible NS1 oestrogen receptor fusion-protein (NS1ERT) in mammalian cells. Upon tamoxifen stimulation, NS1ERT expressing cells partially rescued the attenuated replication of NS1-deficient IAVs and also inhibited interferon up-regulation, confirming the functional competence of NS1ERT. Tamoxifen induced NS1ERT created a cytopathic phenotype and led to the activation of JNK and apoptosis. Induction of NS1F103SERT mutant failed to activate JNK, but induced apoptosis, while the induction of NS1M106IERT led to JNK phosphorylation, but not apoptosis, indicating that JNK activation and apoptosis induction are not functionally linked. Further mutational analysis highlighted that apoptosis induction is a function of the C-terminal effector domain of NS1. Finally, IAVs encoding mutant NS1 revealed a modulating effect of NS1 on apoptosis induction in a genuine infection. With respect to apoptogenicity, a NS1 mutant virus that results in a super-activation of JNK behaves similarly to the JNK non-activating virus expressing NS1F103S, thus confirming that NS1-mediated JNK activation and apoptosis induction are also functionally independent from each other in vivo.
This article is protected by copyright. All rights reserved.
PMID: 28076660 DOI: 10.1111/cmi.12721
[PubMed - as supplied by publisher]
[h=1]Influenza A virus NS1 protein-induced JNK activation and apoptosis are not functionally linked.[/h] Nacken W[SUP]1[/SUP], Wixler V[SUP]1[/SUP], Ehrhardt C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Ludwig S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Expression of the influenza A virus (IAV) non-structural protein NS1 results in the activation of c-Jun N-terminal kinase (JNK). Both NS1 and JNK are involved in apoptosis induction. To investigate their interrelationship, we stably expressed a tamoxifen inducible NS1 oestrogen receptor fusion-protein (NS1ERT) in mammalian cells. Upon tamoxifen stimulation, NS1ERT expressing cells partially rescued the attenuated replication of NS1-deficient IAVs and also inhibited interferon up-regulation, confirming the functional competence of NS1ERT. Tamoxifen induced NS1ERT created a cytopathic phenotype and led to the activation of JNK and apoptosis. Induction of NS1F103SERT mutant failed to activate JNK, but induced apoptosis, while the induction of NS1M106IERT led to JNK phosphorylation, but not apoptosis, indicating that JNK activation and apoptosis induction are not functionally linked. Further mutational analysis highlighted that apoptosis induction is a function of the C-terminal effector domain of NS1. Finally, IAVs encoding mutant NS1 revealed a modulating effect of NS1 on apoptosis induction in a genuine infection. With respect to apoptogenicity, a NS1 mutant virus that results in a super-activation of JNK behaves similarly to the JNK non-activating virus expressing NS1F103S, thus confirming that NS1-mediated JNK activation and apoptosis induction are also functionally independent from each other in vivo.
This article is protected by copyright. All rights reserved.
PMID: 28076660 DOI: 10.1111/cmi.12721
[PubMed - as supplied by publisher]