TRANSFERRIN RECEPTOR 1 IS A CELLULAR RECEPTOR FOR NEW WORLD HEMORRHAGIC FEVER AR

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 至少有五种沙粒病毒引起人类病毒性出血热。拉沙病毒是一种旧大陆沙粒病毒，利用细胞受体α-肌营养不良蛋白聚糖感染细胞1。Machupo、Guanarito、朱宁和Sabia病毒是不使用α-肌营养不良聚糖2的新世界出血热病毒。在这里，我们证明了转铁蛋白受体1（TfR 1）和入口糖蛋白（GP）的马丘波病毒之间的一个特定的，高亲和力的协会。人转铁蛋白受体1，但不是人转铁蛋白受体2，在仓鼠细胞系中的表达显着增强病毒假型与GP的Machupo和朱宁病毒的感染，但不是拉沙或淋巴细胞性脉络丛脑膜炎病毒。抗TfR 1抗体有效抑制Machupo、Guanarito、朱宁和Sabia病毒的复制，但不抑制拉沙病毒的复制。培养基中铁的消耗增强了朱宁和马丘波的感染效率，而铁的补充降低了感染效率，但拉沙假病毒没有。这些数据表明TfR 1是新世界出血热沙粒病毒的细胞受体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. At least five arenaviruses cause viral hemorrhagic fevers in humans. Lassa virus, an Old World arenavirus, utilizes the cellular receptor a-dystroglycan to infect cells1. Machupo, Guanarito, Junin, and Sabia viruses are New World hemorrhagic fever viruses that do not use a-dystroglycan2. Here we demonstrate a specific, high-affinity association between transferrin receptor 1 (TfR1) and the entry glycoprotein (GP) of Machupo virus. Expression of human TfR1, but not human transferrin receptor 2, in hamster cell lines markedly enhanced infection of viruses pseudotyped with the GP of Machupo and Junin viruses, but not Lassa or lymphocytic choriomeningitis viruses. An anti-TfR1 antibody efficiently inhibited replication of Machupo, Guanarito, Junin, and Sabia viruses, but not that of Lassa virus. Iron depletion of culture media enhanced, and iron supplementation reduced, the efficiency of infection by Junin and Machupo but not Lassa pseudoviruses. These data indicate that TfR1 is a cellular receptor for New World hemorrhagic fever arenaviruses.