tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2015 Oct 5. [Epub ahead of print]
[h=1]Bik Mediates Caspase-dependent Cleavage of Viral Proteins to Promote Influenza A Virus Infection.[/h] Mebratu YA[SUP]1[/SUP], Tipper J[SUP]2[/SUP], Chand HS[SUP]3[/SUP], Walton S[SUP]4[/SUP], Harrod KS[SUP]5[/SUP], Tesfaigzi Y[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus induces apoptosis in infected cells to promote viral replication by manipulating the host cell death signaling pathway. While some Bcl-2 family of proteins plays a role in the replication of influenza A virus (IAV), the role of cell death pathways in the viral replication cycle is unclear. We investigated whether deficiency of the pro-apoptotic Bcl-2 family protein, Bik, plays a role in IAV replication. IAV replication was attenuated in mouse airway epithelial cells (MAECs) from bik-/- compared to bik+/+ mice, as indicated by reduced viral titers. Bik-/- MAECs showed more stable trans-epithelial resistance following infection than bik+/+ MAECs, were less sensitive to infection-induced cell death, and released fewer copies of viral RNA. Similar results were obtained when Bik expression was suppressed in human airway epithelial cells (HAECs). Bik+/+ mice drastically lost weight and died within 8 days of infection, while 75% of bik / mice survived infection for 14 days and were 10-fold less likely to die from infection compared to bik+/+ mice. IAV infection activated caspase 3 in bik+/+ but not in bik-/- MAECs and cleavage of viral NP and M2 proteins was absent in bik-/- MAECs and when caspase activation was inhibited in HAECs. Furthermore, Bik deficiency impaired cytoplasmic export of viral RNPs. These studies suggest a link between Bik mediated caspase activation and cleavage of viral proteins. Thus, inhibition of pro-apoptotic host factors such as Bik and downstream mediators of cell death may represent a novel approach for influenza treatment.
[h=4]KEYWORDS:[/h] Bcl-2 family protein; Bik; Influenza A virus infection; caspase; mice
PMID: 26437021 [PubMed - as supplied by publisher]
[h=1]Bik Mediates Caspase-dependent Cleavage of Viral Proteins to Promote Influenza A Virus Infection.[/h] Mebratu YA[SUP]1[/SUP], Tipper J[SUP]2[/SUP], Chand HS[SUP]3[/SUP], Walton S[SUP]4[/SUP], Harrod KS[SUP]5[/SUP], Tesfaigzi Y[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus induces apoptosis in infected cells to promote viral replication by manipulating the host cell death signaling pathway. While some Bcl-2 family of proteins plays a role in the replication of influenza A virus (IAV), the role of cell death pathways in the viral replication cycle is unclear. We investigated whether deficiency of the pro-apoptotic Bcl-2 family protein, Bik, plays a role in IAV replication. IAV replication was attenuated in mouse airway epithelial cells (MAECs) from bik-/- compared to bik+/+ mice, as indicated by reduced viral titers. Bik-/- MAECs showed more stable trans-epithelial resistance following infection than bik+/+ MAECs, were less sensitive to infection-induced cell death, and released fewer copies of viral RNA. Similar results were obtained when Bik expression was suppressed in human airway epithelial cells (HAECs). Bik+/+ mice drastically lost weight and died within 8 days of infection, while 75% of bik / mice survived infection for 14 days and were 10-fold less likely to die from infection compared to bik+/+ mice. IAV infection activated caspase 3 in bik+/+ but not in bik-/- MAECs and cleavage of viral NP and M2 proteins was absent in bik-/- MAECs and when caspase activation was inhibited in HAECs. Furthermore, Bik deficiency impaired cytoplasmic export of viral RNPs. These studies suggest a link between Bik mediated caspase activation and cleavage of viral proteins. Thus, inhibition of pro-apoptotic host factors such as Bik and downstream mediators of cell death may represent a novel approach for influenza treatment.
[h=4]KEYWORDS:[/h] Bcl-2 family protein; Bik; Influenza A virus infection; caspase; mice
PMID: 26437021 [PubMed - as supplied by publisher]