Lassa virus entry requires a trigger-induced receptor switch

Lucas T. Jae, Matthijs Raaben, Andrew S. Herbert, Ana I. Kuehne, Ariel S. Wirchnianski, Timothy K. Soh, Sarah H. Stubbs, Hans Janssen, Markus Damme, Paul Saftig, Sean P. Whelan, John M. Dye, Thijn R. Brummelkamp

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

Abstract

Lassa virus spreads from a rodent to humans and can lead to lethal hemorrhagic fever. Despite its broad tropism, chicken cells were reported 30 years ago to resist infection. We found that Lassa virus readily engaged its cell-surface receptor α-dystroglycan in avian cells, but virus entry in susceptible species involved a pH-dependent switch to an intracellular receptor, the lysosome-resident protein LAMP1. Iterative haploid screens revealed that the sialyltransferase ST3GAL4 was required for the interaction of the virus glycoprotein with LAMP1. A single glycosylated residue in LAMP1, present in susceptible species but absent in birds, was essential for interaction with the Lassa virus envelope protein and subsequent infection. The resistance of Lamp1-deficient mice to Lassa virus highlights the relevance of this receptor switch in vivo.

Original languageEnglish
Pages (from-to)1506-1510
Number of pages5
JournalScience
Volume344
Issue number6191
DOIs
StatePublished - 2014

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