tetano
Editor, Senior Moderator
PLoS One
. 2020 May 15;15(5):e0233052.
doi: 10.1371/journal.pone.0233052. eCollection 2020.
The Influenza Replication Blocking Inhibitor LASAG Does Not Sensitize Human Epithelial Cells for Bacterial Infections
Janine J Wilden[SUP] 1 [/SUP], Andre van Kr?chten[SUP] 1 [/SUP], Lutz Gieselmann[SUP] 1 [/SUP], Eike R Hrincius[SUP] 1 [/SUP], Stefanie Deinhardt-Emmer[SUP] 2 [/SUP], Karoline F Haupt[SUP] 2 [/SUP], Hannah F Preugschas[SUP] 1 [/SUP], Silke Niemann[SUP] 3 [/SUP], Stephan Ludwig[SUP] 1 4 [/SUP], Christina Ehrhardt[SUP] 1 2 [/SUP]
Affiliations
Abstract
Severe influenza virus (IV) infections still represent a major challenge to public health. To combat IV infections, vaccines and antiviral compounds are available. However, vaccine efficacies vary with very limited to no protection against newly emerging zoonotic IV introductions. In addition, the development of resistant virus variants against currently available antivirals can be rapidly detected, in consequence demanding the design of novel antiviral strategies. Virus supportive cellular signaling cascades, such as the NF-κB pathway, have been identified to be promising antiviral targets against IV in in vitro and in vivo studies and clinical trials. While administration of NF-κB pathway inhibiting agents, such as LASAG results in decreased IV replication, it remained unclear whether blocking of NF-κB might sensitize cells to secondary bacterial infections, which often come along with viral infections. Thus, we examined IV and Staphylococcus aureus growth during LASAG treatment. Interestingly, our data reveal that the presence of LASAG during superinfection still leads to reduced IV titers. Furthermore, the inhibition of the NF-κB pathway resulted in decreased intracellular Staphylococcus aureus loads within epithelial cells, indicating a dependency on the pathway for bacterial uptake. Unfortunately, so far it is not entirely clear if this phenomenon might be a drawback in bacterial clearance during infection.
. 2020 May 15;15(5):e0233052.
doi: 10.1371/journal.pone.0233052. eCollection 2020.
The Influenza Replication Blocking Inhibitor LASAG Does Not Sensitize Human Epithelial Cells for Bacterial Infections
Janine J Wilden[SUP] 1 [/SUP], Andre van Kr?chten[SUP] 1 [/SUP], Lutz Gieselmann[SUP] 1 [/SUP], Eike R Hrincius[SUP] 1 [/SUP], Stefanie Deinhardt-Emmer[SUP] 2 [/SUP], Karoline F Haupt[SUP] 2 [/SUP], Hannah F Preugschas[SUP] 1 [/SUP], Silke Niemann[SUP] 3 [/SUP], Stephan Ludwig[SUP] 1 4 [/SUP], Christina Ehrhardt[SUP] 1 2 [/SUP]
Affiliations
- PMID: 32413095
- DOI: 10.1371/journal.pone.0233052
Abstract
Severe influenza virus (IV) infections still represent a major challenge to public health. To combat IV infections, vaccines and antiviral compounds are available. However, vaccine efficacies vary with very limited to no protection against newly emerging zoonotic IV introductions. In addition, the development of resistant virus variants against currently available antivirals can be rapidly detected, in consequence demanding the design of novel antiviral strategies. Virus supportive cellular signaling cascades, such as the NF-κB pathway, have been identified to be promising antiviral targets against IV in in vitro and in vivo studies and clinical trials. While administration of NF-κB pathway inhibiting agents, such as LASAG results in decreased IV replication, it remained unclear whether blocking of NF-κB might sensitize cells to secondary bacterial infections, which often come along with viral infections. Thus, we examined IV and Staphylococcus aureus growth during LASAG treatment. Interestingly, our data reveal that the presence of LASAG during superinfection still leads to reduced IV titers. Furthermore, the inhibition of the NF-κB pathway resulted in decreased intracellular Staphylococcus aureus loads within epithelial cells, indicating a dependency on the pathway for bacterial uptake. Unfortunately, so far it is not entirely clear if this phenomenon might be a drawback in bacterial clearance during infection.