Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses
Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses
复制标题
DOI：
10.1371/journal.ppat.1000358
复制
发表时间：
2009-04-01
期刊：
影响因子：
6.7
通讯作者：
Choe, Hyeryun
中科院分区：
文献类型：
--
作者：
Abraham, Jonathan;Kwong, Jo Ann;Choe, Hyeryun
新世界（NW） B支沙粒病毒通过人转铁蛋白受体1 （TfR1）进入细胞的能力与其引起出血热的能力密切相关。Amapari （AMAV）和Tacaribe （TCRV）是两种不使用人类TfR1的非致病性NW进化支B沙粒病毒，与引起出血热的NW沙粒病毒密切相关。本研究表明，携带AMAV或TCRV表面糖蛋白（GP）的假型病毒可以通过几种哺乳动物物种的TfR1同源物感染细胞，包括它们各自的天然宿主，小型啮齿动物Neacomys spinosus和果蝠Artibeus牙买加人。人TfR1中一个残基的突变使其成为TCRV的功能性受体，四个残基的突变使其成为AMAV的功能性受体。我们的数据支持TfR1在大多数（如果不是全部的话）NW分支B沙粒病毒的体内复制中发挥作用，并表明非致病性沙粒病毒可以利用人类TfR1并作为人类病原体出现。
The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens.