Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation.

Abstract:

: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.

authors

de Greef JC,Slütter B,Anderson ME,Hamlyn R,O'Campo Landa R,McNutt EJ,Hara Y,Pewe LL,Venzke D,Matsumura K,Saito F,Harty JT,Campbell KP

doi

10.1073/pnas.1904493116

subject

Has Abstract

pub_date

2019-06-04 00:00:00

pages

11396-11401

issue

23

eissn

0027-8424

issn

1091-6490

pii

1904493116

journal_volume

116

pub_type

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