Publication in Science

Science

Lassa Virus unravels a unique sugar layer in human brain and muscle; Science, March 22, 2013

The cellular entry receptor for the hemorrhagic fever-causing Lassa virus is a unique and unsolved glycan structure on the dystroglycan protein. In human, this glycan binds to extracellular ligands in muscle, eye and brain and causes severe disease when defective. In the current issue of Science, Lucas Jae and Thijn Brummelkamp (Netherlands Cancer Institute), in collaboration with Moniek Riemersma, Ellen van Beusekom, Dirk Lefeber and Hans van Bokhoven, have cracked the genetic code required for generating this unique glycan. A genome-wide genetic screen was performed in human cells using Lassa virus and glycan-specific antibodies to select mutant cells. A large set of 15 genes was identified, including all known and 6 new genes. TALEN technology was applied to generate well-defined knock-out cells of the new genes for functional confirmation. The generated knowledge paves the way for further structural and functional studies.

Deciphering the Glycosylome of Dystroglycanopathies Using Haploid Screens for Lassa Virus Entry
Jae LT, Raaben M, Riemersma M, van Beusekom E, Blomen VA, Velds A, Kerkhoven RM, Carette JE, Topaloglu H, Meinecke P, Wessels MW, Lefeber DJ, Whelan SP, van Bokhoven H, Brummelkamp TR.
Science. 2013 Mar 21. [Epub ahead of print]

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