tetano
Editor, Senior Moderator
Antiviral Res. 2015 Sep 11. pii: S0166-3542(15)00216-8. doi: 10.1016/j.antiviral.2015.09.005. [Epub ahead of print]
[h=1]Interleukin-24 inhibits influenza A virus replication in vitro through induction of toll-like receptor 3 dependent apoptosis.[/h] Weiss R[SUP]1[/SUP], Laengle J[SUP]1[/SUP], Sachet M[SUP]1[/SUP], Shurygina AP[SUP]2[/SUP], Kiselev O[SUP]2[/SUP], Egorov A[SUP]2[/SUP], Bergmann M[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] New anti-viral agents and strategies are urgently needed to fight rapidly mutating viruses, as vaccine programs cannot react fast enough to prevent pandemics. Recently, we have shown that interleukin-24 (IL-24) sensitizes tumor cells to toll-like receptor 3 (TLR3) mediated apoptosis. As influenza A virus stimulates the TLR3 receptor, we hypothesized that IL-24 might also exert an anti-viral effect. This study demonstrates that IL-24 reduces the titer of different influenza A virus subtypes independently of type I interferon in an apoptosis dependent manner. The anti-viral effect of IL-24 correlated with caspase-3 activation and could be blocked by a pan-caspase inhibitor and by small interfering RNA (siRNA) directed towards TLR3. Surprisingly, caspase-3 activation in influenza A virus/IL-24-stimulated cells correlated with the down-regulation of the B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia 1 (Mcl-1). Correspondingly, knockdown of Mcl-1 by siRNA enhanced caspase activation in influenza A virus infected cells and was furthermore linked to a reduction of viral titers. We conclude that IL-24 exerts an anti-viral role selectively purging virally infected cells by leading to a down-regulation of Mcl-1. Our findings might therefore represent the first step towards a new rational concept in the development of anti-viral strategies based on the induction of apoptosis.
Copyright ? 2015 Elsevier B.V. All rights reserved.
[h=4]KEYWORDS:[/h] Apoptosis; Caspase-3; Influenza A virus; Interleukin-24; Myeloid cell leukemia 1; Toll-like receptor 3
PMID: 26367324 [PubMed - as supplied by publisher]
[h=1]Interleukin-24 inhibits influenza A virus replication in vitro through induction of toll-like receptor 3 dependent apoptosis.[/h] Weiss R[SUP]1[/SUP], Laengle J[SUP]1[/SUP], Sachet M[SUP]1[/SUP], Shurygina AP[SUP]2[/SUP], Kiselev O[SUP]2[/SUP], Egorov A[SUP]2[/SUP], Bergmann M[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] New anti-viral agents and strategies are urgently needed to fight rapidly mutating viruses, as vaccine programs cannot react fast enough to prevent pandemics. Recently, we have shown that interleukin-24 (IL-24) sensitizes tumor cells to toll-like receptor 3 (TLR3) mediated apoptosis. As influenza A virus stimulates the TLR3 receptor, we hypothesized that IL-24 might also exert an anti-viral effect. This study demonstrates that IL-24 reduces the titer of different influenza A virus subtypes independently of type I interferon in an apoptosis dependent manner. The anti-viral effect of IL-24 correlated with caspase-3 activation and could be blocked by a pan-caspase inhibitor and by small interfering RNA (siRNA) directed towards TLR3. Surprisingly, caspase-3 activation in influenza A virus/IL-24-stimulated cells correlated with the down-regulation of the B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia 1 (Mcl-1). Correspondingly, knockdown of Mcl-1 by siRNA enhanced caspase activation in influenza A virus infected cells and was furthermore linked to a reduction of viral titers. We conclude that IL-24 exerts an anti-viral role selectively purging virally infected cells by leading to a down-regulation of Mcl-1. Our findings might therefore represent the first step towards a new rational concept in the development of anti-viral strategies based on the induction of apoptosis.
Copyright ? 2015 Elsevier B.V. All rights reserved.
[h=4]KEYWORDS:[/h] Apoptosis; Caspase-3; Influenza A virus; Interleukin-24; Myeloid cell leukemia 1; Toll-like receptor 3
PMID: 26367324 [PubMed - as supplied by publisher]