CD164 is a host factor for lymphocytic choriomeningitis virus entry
Mark J. G. Bakkers, Alex Moon-Walker, Rasmus Herlo, Vesna Brusic, Sarah H. Stubbs, Kathryn M. Hastie, Erica Ollmann Saphire, Tomas Kirchhausen, Sean P. J. Whelan
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.