LAUSR

Significance Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and has been utilized for decades as a model to understand the host immune response against viral infection. LCMV infection can lead to fatal meningitis in immunocompromised people and can lead to congenital birth defects and spontaneous abortion if acquired during pregnancy. Using a genetic screen, we uncover host factors involved in LCMV entry that were previously unknown and are candidate therapeutic targets to combat LCMV infection. This study expands our understanding of the entry pathway of LCMV, revealing that its glycoprotein switches from utilizing the known receptor α-DG and heparan sulfate at the plasma membrane to binding the lysosomal mucin CD164 at pH levels found in endolysosomal compartments, facilitating membrane fusion.