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

by Carette, Jan E. , Lefeber, Dirk J. , Meinecke, Peter , Blomen, Vincent A. , Wessels, Marja W. , Whelan, Sean P. , Velds, Arno , Jae, Lucas T. , van Beusekom, Ellen , van Bokhoven, Hans , Raaben, Matthijs , Brummelkamp, Thijn R. , Riemersma, Moniek , Topaloglu, Haluk , Kerkhoven, Ron. M.

in Amino Acid Sequence / Cell Line / Cell lines / Cellular / Cellular biology / congenital abnormalities / Disorders / Dystroglycans - metabolism / Female / Genes / Genetic mutation / Genetics / Glycoproteins / Glycosylation / Haploidy / Host-Pathogen Interactions - genetics / Humans / Infant / Integration host factors / Lassa Fever - genetics / Lassa Fever - virology / Lassa mammarenavirus / Lassa virus / Lassa virus - physiology / Male / Membrane Proteins - genetics / Molecular Sequence Data / Mutation / Mutations / Online / Pedigree / Proteome - metabolism / Screens / Sulfates / Viral infections / Virus Internalization / Viruses / Walker Warburg syndrome / Walker-Warburg Syndrome - genetics

2013

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

2013

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

2013

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Journal Article

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

Carette, Jan E.,

Lefeber, Dirk J.,

Meinecke, Peter,

Blomen, Vincent A.,

Wessels, Marja W.,

Whelan, Sean P.,

Velds, Arno,

Jae, Lucas T.,

van Beusekom, Ellen,

van Bokhoven, Hans,

Raaben, Matthijs,

Brummelkamp, Thijn R.,

Riemersma, Moniek,

Topaloglu, Haluk,

Kerkhoven, Ron. M.

2013

Overview

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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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

/ congenital abnormalities

/ Disorders