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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.