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

被引：10

作者：

de Greef, Jessica C. ^{[1
,2
,3
]}

Slutter, Bram ^{[4
]}

Anderson, Mary E. ^{[1
,2
,3
]}

Hamlyn, Rebecca ^{[1
,2
,3
]}

Landa, Raul O'Campo ^{[1
,2
,3
]}

McNutt, Ellison J. ^{[1
,2
,3
]}

Hara, Yuji ^{[1
,2
,3
]}

Pewe, Lecia L. ^{[4
]}

Venzke, David ^{[1
,2
,3
]}

Matsumura, Kiichiro ^{[5
]}

Saito, Fumiaki ^{[5
]}

Harty, John T. ^{[4
,6
]}

Campbell, Kevin P. ^{[1
,2
,3
]}

机构：

[1] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA

[2] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA

[3] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA

[4] Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA 52242 USA

[5] Teikyo Univ, Sch Med, Dept Neurol, Tokyo 1738605, Japan

[6] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2019年 / 116卷 / 23期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

alpha-dystroglycan; influenza A virus; inflammation; GLYCOPROTEIN-COMPLEX; DYSTROPHIN; FURIN; DISRUPTION; MEMBRANE; LAMININ; BINDING; REGION; SITE; IDENTIFICATION;

D O I：

10.1073/pnas.1904493116

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：11396 / 11401

页数：6

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