tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2019 May 16. pii: 201904493. doi: 10.1073/pnas.1904493116. [Epub ahead of print]
[h=1]Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation.[/h] de Greef JC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Sl?tter B[SUP]4[/SUP], Anderson ME[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Hamlyn R[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], O'Campo Landa R[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], McNutt EJ[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Hara Y[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Pewe LL[SUP]4[/SUP], Venzke D[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Matsumura K[SUP]5[/SUP], Saito F[SUP]5[/SUP], Harty JT[SUP]4,[/SUP][SUP]6[/SUP], Campbell KP[SUP]7,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2019 the Author(s). Published by PNAS.
[h=4]KEYWORDS:[/h] inflammation; influenza A virus; α-dystroglycan
PMID: 31097590 DOI: 10.1073/pnas.1904493116
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[h=1]Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation.[/h] de Greef JC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Sl?tter B[SUP]4[/SUP], Anderson ME[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Hamlyn R[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], O'Campo Landa R[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], McNutt EJ[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Hara Y[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Pewe LL[SUP]4[/SUP], Venzke D[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Matsumura K[SUP]5[/SUP], Saito F[SUP]5[/SUP], Harty JT[SUP]4,[/SUP][SUP]6[/SUP], Campbell KP[SUP]7,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2019 the Author(s). Published by PNAS.
[h=4]KEYWORDS:[/h] inflammation; influenza A virus; α-dystroglycan
PMID: 31097590 DOI: 10.1073/pnas.1904493116
Free full text