title: Transferrin Receptor 1 Facilitates Poliovirus Permeation of Mouse Brain Capillary Endothelial Cells.
abstract: As a possible route for invasion of the CNS, circulating poliovirus (PV) in the blood is believed to traverse the blood-brain barrier (BBB), resulting in paralytic poliomyelitis. However, the underlying mechanism is poorly understood. In this study, we demonstrated that mouse transferrin receptor 1 (mTfR1) is responsible for PV attachment to the cell surface, allowing invasion into the CNS via the BBB. PV interacts with the apical domain of mTfR1 on mouse brain capillary endothelial cells (MBEC4) in a dose-dependent manner via its capsid protein (VP1). We found that F-G, G-H, and H-I loops in VP1 are important for this binding. However, C-D, D-E, and E-F loops in VP1-fused Venus proteins efficiently penetrate MBEC4 cells. These results imply that the VP1 functional domain responsible for cell attachment is different from that involved in viral permeation of the brain capillary endothelium. We observed that co-treatment of MBEC4 cells with excess PV particles but not dextran resulted in blockage of transferrin transport into cells. Using the Transwell in vitro BBB model, transferrin co-treatment inhibited permeation of PV into MBEC4 cells and delayed further viral permeation via mTfR1 knockdown. With mTfR1 as a positive mediator of PV-host cell attachment and PV permeation of MBEC4 cells, our results indicate a novel role of TfR1 as a cellular receptor for human PV receptor/CD155-independent PV invasion of the CNS.
authors.affiliation: From the Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan mizutanit@bikaken.or.jp.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: From the Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ishizaka
authors.affiliation: From the Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
authors.forename: Coh-Ichi
authors.initials: C
authors.lastname: Nihei
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D036022:Capsid Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D017955:Poliovirus / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; C442540:VP1 protein, Poliovirus
keywords: blood brain barrier; cell adhesion; cell permeabilization; intracellular trafficking; molecular biology; transferrin