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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 至少有五种禽流感病毒会导致人类病毒性出血热。拉萨病毒是一种东半球阿雷纳病毒，它利用细胞受体α-肌营养不良聚糖感染细胞1。Machupo、Guanarito、Junin和Sabia病毒是新世界出血热病毒，不使用α-dystrocan2。在这里，我们展示了转铁蛋白受体1(TfR1)和马丘波病毒的进入糖蛋白(GP)之间的特异性和高亲和力的联系。在仓鼠细胞系中表达人转铁蛋白受体2，但不表达人转铁蛋白受体2，显著增强了与Machupo和Junin病毒GP假型病毒的感染，但不能促进LassA或淋巴细胞性脉络膜脑膜炎病毒的感染。抗TfR1抗体有效地抑制了Machupo、Guanarito、Junin和Sabia病毒的复制，但不能抑制Lassa病毒的复制。培养基铁消耗增加，补铁减少，感染Junin和Machupo病毒的效率增加，但不能感染Lassa伪病毒。这些数据表明，TfR1是新世界出血热病毒的细胞受体。

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.