CD164 is a host factor for lymphocytic choriomeningitis virus entry.
Mark J G BakkersAlex Moon-WalkerRasmus HerloVesna BrusicSarah Hulsey StubbsKathryn M HastieErica Ollmann SaphireTomas L KirchhausenSean P J WhelanPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
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.