CD164 is a host factor for lymphocytic choriomeningitis virus entry

Mark J.G. Bakkers, Alex Moon-Walker, Rasmus Herlo, Vesna Brusic, Sarah Hulsey Stubbs, Kathryn M. Hastie, Erica Ollmann Saphire, Tomas L. Kirchhausen, Sean P.J. Whelan

Research output: Contribution to journalArticlepeer-review

Abstract

Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne zoonotic arenavirus that causes congenital abnormalities and can be fatal for transplant recipients. Using a genome-wide loss-of-function screen, we identify host factors required for LCMV entry into cells. We identify the lysosomal mucin CD164, glycosylation factors, the heparan sulfate biosynthesis machinery, and the known receptor alpha-dystroglycan (α-DG). Biochemical analysis revealed that the LCMV glycoprotein binds CD164 at acidic pH and requires a sialylated glycan at residue N104. We demonstrate that LCMV entry proceeds by the virus switching binding from heparan sulfate or α-DG at the plasma membrane to CD164 prior to membrane fusion, thus identifying additional potential targets for therapeutic intervention.

Original languageEnglish
Article numbere2119676119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number10
DOIs
StatePublished - Mar 8 2022

Keywords

  • CD164
  • arenavirus
  • lymphocytic choriomeningitis virus
  • virus entry

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