Protein Kinase D: A new target in the fight against flu?
| Autor: | Janelle Veazey, Timothy J Chapman, Timothy R Smyth, Sara E Hillman, Sophia I Eliseeva, Steve N Georas |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:245.13-245.13 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.245.13 |
| Popis: | Summary Antivirals targeting host proteins may slow development of viral resistance and work against multiple viruses. The serine/threonine kinase protein kinase D (PKD) is one promising target as others have shown inhibiting PKD restricts rhinovirus and hepatitis in cell culture. We show inhibiting PKD restricts Influenza A virus (IAV) in cell culture and in mice. Methods The competitive PKD inhibitor, CRT, was given to A549, 16HBE cells and mice, prior to or during stimulation with dsRNA or IAV. Pulmonary barrier integrity was quantified by assaying total protein leak into the lumen (inside/out leak), and loss of 4kDa FITC-dextran out of the lumen (outside/in leak). Inflammatory cytokine levels were determined via ELISA/multiplex and mRNA levels via RT-PCR. Transcription factor activity was assayed via luciferase reporter system. Viral load was determined via RT-PCR of viral M protein. For in vivo IAV experiments, mice were given CRT/vehicle post-infection with lethal dose IAV (PR/8) and morbidity assessed by weight loss. Results Conclusion PKD inhibition promotes barrier integrity, lowers transcription of potentially pathogenic pro-inflammatory cytokines, and restricts viral replication, highlighting the potential of CRT as a novel anti-viral therapeutic. |
| Databáze: | OpenAIRE |
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