Protective role for the N-terminal domain of α-dystroglycan in #Influenza A virus #proliferation (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

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

Jessica C. de Greef, Bram Slütter, Mary E. Anderson, Rebecca Hamlyn, Raul O’Campo Landa, Ellison J. McNutt, Yuji Hara, Lecia L. Pewe, David Venzke, Kiichiro Matsumura, Fumiaki Saito, John T. Harty, and Kevin P. Campbell

PNAS first published May 16, 2019 / DOI: https://doi.org/10.1073/pnas.1904493116

Contributed by Kevin P. Campbell, April 16, 2019 (sent for review March 20, 2019; reviewed by Andrea Brancaccio and Jamey D. Marth)

 

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.

 

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.

α-dystroglycan – influenza A virus – inflammation

Keywords: Influenza A; Immunopathology; Viral Pathogenesis.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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