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


Jae L. T. , Raaben M., Riemersma M., van Beusekom E., Blomen V. A. , Velds A., ...More

SCIENCE, vol.340, no.6131, pp.479-483, 2013 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 340 Issue: 6131
  • Publication Date: 2013
  • Doi Number: 10.1126/science.1233675
  • Title of Journal : SCIENCE
  • Page Numbers: pp.479-483

Abstract

Glycosylated alpha-dystroglycan (alpha-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 alpha-DG, but many genes mutated in WWS remain unknown. To identify modifiers of alpha-DG, we performed a haploid screen for Lassa virus entry, a hemorrhagic fever virus causing thousands of deaths annually that hijacks glycosylated alpha-DG to enter cells. In complementary screens, we profiled cells for absence of alpha-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 alpha-DG. Our findings accentuate the complexity of this posttranslational feature and point out genes defective in dystroglycanopathies.