| First Author | de Greef JC | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 23 | Pages | 11396-11401 |
| PubMed ID | 31097590 | Mgi Jnum | J:276543 |
| Mgi Id | MGI:6314172 | Doi | 10.1073/pnas.1904493116 |
| Citation | de Greef JC, et al. (2019) Protective role for the N-terminal domain of alpha-dystroglycan in Influenza A virus proliferation. Proc Natl Acad Sci U S A 116(23):11396-11401 |
| abstractText | alpha-Dystroglycan (alpha-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (alpha-DGN). Before cleavage, alpha-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of alpha-DG. Notably, alpha-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted alpha-DGN remains unknown. Here, we show that mice lacking alpha-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 alpha-DGN before infection or intranasal treatment with recombinant alpha-DGN prior and during infection, significantly reduced IAV titers in the lungs of wild-type mice. Hemagglutination inhibition assays using recombinant alpha-DGN showed in vitro neutralization of IAV. Collectively, our results support a protective role for alpha-DGN in IAV proliferation. |
