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

doi:10.1126/science.1252480

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 journal › Article › peer-review

181 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 language	English
Pages (from-to)	1506-1510
Number of pages	5
Journal	Science
Volume	344
Issue number	6191
DOIs	https://doi.org/10.1126/science.1252480
State	Published - 2014

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title = "Lassa virus entry requires a trigger-induced receptor switch",

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.",

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

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T1 - Lassa virus entry requires a trigger-induced receptor switch

AU - Jae, Lucas T.

AU - Raaben, Matthijs

AU - Herbert, Andrew S.

AU - Kuehne, Ana I.

AU - Wirchnianski, Ariel S.

AU - Soh, Timothy K.

AU - Stubbs, Sarah H.

AU - Janssen, Hans

AU - Damme, Markus

AU - Saftig, Paul

AU - Whelan, Sean P.

AU - Dye, John M.

AU - Brummelkamp, Thijn R.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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Lassa virus entry requires a trigger-induced receptor switch

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