Report

Deciphering the Glycosylome of Dystroglycanopathies Using Haploid Screens for Lassa Virus Entry

Science  21 Mar 2013:

DOI: 10.1126/science.1233675

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

Glycosylated alpha-dystroglycan (α-DG) serves as cellular entry receptor for multiple pathogens, and defects in its glycosylation cause hereditary Walker-Warburg syndrome (WWS). At least eight proteins are critical to glycosylate α-DG, but many genes mutated in WWS remain unknown. To identify modifiers of α-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated α-DG to enter cells. In complementary screens, we profiled cells for absence of α-DG carbohydrate chains or biochemically related glycans. This revealed virus host factors and a suite of glycosylation units, including all known Walker-Warburg genes and five additional factors critical for the modification of α-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.

View Full Text

Cited By...