The influenza replication blocking inhibitor LASAG does not sensitize human epithelial cells for bacterial infections
| Autor: | Janine J. Wilden, Christina Ehrhardt, Lutz Gieselmann, Andre van Krüchten, Eike R. Hrincius, Stefanie Deinhardt-Emmer, Hannah F. Preugschas, Stephan Ludwig, Silke Niemann, Karoline Frieda Haupt |
|---|---|
| Přispěvatelé: | Universitäts- und Landesbibliothek Münster |
| Rok vydání: | 2020 |
| Předmět: |
Bacterial Diseases
0301 basic medicine Physiology Staphylococcus Virus Replication Pathology and Laboratory Medicine medicine.disease_cause Biochemistry Epithelium Influenza A Virus H1N1 Subtype Animal Cells Immune Physiology Medicine and Health Sciences Influenza A virus Small interfering RNAs Staphylococcus Aureus Innate Immune System Multidisciplinary NF-kappa B Bacterial Infections Staphylococcal Infections Bacterial Pathogens Nucleic acids Drug Combinations Infectious Diseases Intracellular Pathogens Medical Microbiology Staphylococcus aureus Gene Knockdown Techniques Superinfection Medicine Cytokines Pathogens Cellular Types Anatomy Signal Transduction Research Article Methicillin-Resistant Staphylococcus aureus Cell signaling Science Immunology 030106 microbiology Glycine Biology Antiviral Agents Microbiology Virus 03 medical and health sciences In vivo ddc:570 Virology Influenza Human Genetics medicine Humans Non-coding RNA Microbial Pathogens A549 cell Aspirin Bacteria Lysine Intracellular parasite Transcription Factor RelA Organisms Biology and Life Sciences Epithelial Cells Cell Biology Molecular Development Viral Replication Gene regulation Biological Tissue 030104 developmental biology A549 Cells Immune System RNA Gene expression Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 5, p e0233052 (2020) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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