Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation
| العنوان: | Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation |
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| المؤلفون: | Raul O’Campo Landa, John T. Harty, Jessica C. de Greef, Kevin P. Campbell, Mary E. Anderson, Rebecca Hamlyn, David Venzke, Yuji Hara, Bram Slütter, Kiichiro Matsumura, Fumiaki Saito, Ellison J. McNutt, Lecia L. Pewe |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America |
| بيانات النشر: | National Academy of Sciences, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Medical Sciences, Glycosylation, medicine.disease_cause, Protective Agents, Neutralization, Basement Membrane, Microbiology, law.invention, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, Orthomyxoviridae Infections, law, Influenza, Human, Influenza A virus, medicine, influenza A virus, Animals, Humans, Receptor, Dystroglycans, Furin, Lung, Cell Proliferation, Inflammation, Multidisciplinary, Hemagglutination assay, biology, α-dystroglycan, Biological Sciences, Viral Load, Proprotein convertase, In vitro, 3. Good health, Body Fluids, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, 030220 oncology & carcinogenesis, biology.protein, Recombinant DNA |
| الوصف: | Significance Influenza A virus (IAV) is a major cause of respiratory infections. We show that mice lacking the N-terminal domain of α-dystroglycan (α-DGN) exhibit significantly higher viral titers in the lungs after IAV infection. In addition, we show that overexpression of α-DGN in the lungs, both prior and during IAV infection, significantly reduces viral load and that recombinant α-DGN disrupts hemagglutination mediated by the influenza virus. Collectively, we uncover a protective role for α-DGN in IAV proliferation, suggesting it may have antiviral properties and could potentially be used as a treatment for IAV infection. As α-DGN levels are altered in more (inflammatory) disease states, this insight opens new avenues of investigation into the role of α-DGN in inflammation. α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Notably, α-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted α-DGN remains unknown. Here, we show that mice lacking α-DGN exhibit significantly higher viral titers in the lungs after Influenza A virus (IAV) infection (strain A/Puerto Rico/8/1934 H1N1), suggesting an inability to control virus load. Consistent with this, overexpression of α-DGN before infection or intranasal treatment with recombinant α-DGN prior and during infection, significantly reduced IAV titers in the lungs of wild-type mice. Hemagglutination inhibition assays using recombinant α-DGN showed in vitro neutralization of IAV. Collectively, our results support a protective role for α-DGN in IAV proliferation. |
| اللغة: | English |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c733ec95c7b65a976e14b6cd21d574a http://europepmc.org/articles/PMC6561248 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4c733ec95c7b65a976e14b6cd21d574a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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