Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry

Glycosylated α-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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 340; no. 6131; p. 479
Main Authors: Jae, Lucas T, Raaben, Matthijs, Riemersma, Moniek, van Beusekom, Ellen, Blomen, Vincent A, Velds, Arno, Kerkhoven, Ron M, Carette, Jan E, Topaloglu, Haluk, Meinecke, Peter, Wessels, Marja W, Lefeber, Dirk J, Whelan, Sean P, van Bokhoven, Hans, Brummelkamp, Thijn R
Format: Journal Article
Language:English
Published: United States 26.04.2013
Subjects:
Amino Acid Sequence
Cell Line
Dystroglycans - metabolism
Female
Glycosylation
Haploidy
Host-Pathogen Interactions - genetics
Humans
Infant
Lassa Fever - genetics
Lassa Fever - virology
Lassa virus - physiology
Male
Membrane Proteins - genetics
Molecular Sequence Data
Mutation
Pedigree
Proteome - metabolism
Virus Internalization
Walker-Warburg Syndrome - genetics
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary:Glycosylated α-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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.1233675