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Science. 2014 Jun 27;344(6191):1506-10. doi: 10.1126/science.1252480.

Virus entry. Lassa virus entry requires a trigger-induced receptor switch.

Author information

1
Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands.
2
Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
3
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA.
4
Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
5
Biochemisches Institut, Christian Albrechts-Universität Kiel, 24118 Kiel, Germany.
6
Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu.
7
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu.
8
Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Cancer Genomics Center (CGC.nl), Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. t.brummelkamp@nki.nl john.m.dye1.civ@mail.mil sean_whelan@hms.harvard.edu.

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.

PMID:
24970085
PMCID:
PMC4239993
DOI:
10.1126/science.1252480
[Indexed for MEDLINE]
Free PMC Article

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