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标题：CD164 is a host factor for lymphocytic choriomeningitis virus entry
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作者：Mark J. G. Bakkers ; Alex Moon-Walker ; Rasmus Herlo 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：10
DOI：10.1073/pnas.2119676119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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. 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.
关键词：enlymphocytic choriomeningitis virusCD164arenavirusvirus entry