Radoshitzky Sheli R, Kuhn Jens H, Spiropoulou Christina F, Albariño César G, Nguyen Dan P, Salazar-Bravo Jorge, Dorfman Tatyana, Lee Amy S, Wang Enxiu, Ross Susan R, Choe Hyeryun, Farzan Michael
Department of Microbiology and Molecular Genetics and New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2664-9. doi: 10.1073/pnas.0709254105. Epub 2008 Feb 11.
Transferrin receptor 1 (TfR1) is a cellular receptor for the New World hemorrhagic fever arenaviruses Machupo (MACV), Junín (JUNV), and Guanarito (GTOV). Each of these viruses is specifically adapted to a distinct rodent host species, but all cause human disease. Here we compare the ability of these viruses to use various mammalian transferrin receptor 1 (TfR1) orthologs, including those of the South American rodents that serve as reservoirs for MACV, JUNV, and GTOV (Calomys callosus, Calomys musculinus, and Zygodontomys brevicauda, respectively). Retroviruses pseudotyped with MACV and JUNV but not GTOV glycoproteins (GPs) efficiently used C. callosus TfR1, whereas only JUNV GP could use C. musculinus TfR1. All three viruses efficiently used Z. brevicauda TfR1. TfR1 orthologs from related rodents, including house mouse (Mus musculus) and rat (Rattus norvegicus), did not support entry of these viruses. In contrast, these viruses efficiently used human and domestic cat TfR1 orthologs. We further show that a local region of the human TfR1 apical domain, including tyrosine 211, determined the efficiency with which MACV, JUNV, and GTOV used various TfR1 orthologs. Our data show that these New World arenaviruses are specifically adapted to the TfR1 orthologs of their respective rodent hosts and identify key commonalities between these orthologs and human TfR1 necessary for efficient transmission of these viruses to humans.
转铁蛋白受体1（TfR1）是新大陆出血热沙粒病毒马丘波病毒（MACV）、胡宁病毒（JUNV）和瓜纳里托病毒（GTOV）的细胞受体。这些病毒中的每一种都特异性适应于不同的啮齿动物宿主物种，但都会引发人类疾病。在这里，我们比较了这些病毒利用各种哺乳动物转铁蛋白受体1（TfR1）直系同源物的能力，包括作为MACV、JUNV和GTOV储存宿主的南美啮齿动物（分别为卡氏棉鼠、小家鼠棉鼠和短尾梳趾鼠）的转铁蛋白受体1直系同源物。用MACV和JUNV而非GTOV糖蛋白（GPs）假型化的逆转录病毒能有效利用卡氏棉鼠的TfR1，而只有JUNV GP能利用小家鼠棉鼠的TfR1。所有这三种病毒都能有效利用短尾梳趾鼠的TfR1。来自相关啮齿动物（包括家鼠和大鼠）的TfR1直系同源物不支持这些病毒的进入。相反，这些病毒能有效利用人类和家猫的TfR1直系同源物。我们进一步表明，人类TfR1顶端结构域的一个局部区域，包括酪氨酸211，决定了MACV、JUNV和GTOV利用各种TfR1直系同源物的效率。我们的数据表明，这些新大陆沙粒病毒特异性适应于其各自啮齿动物宿主的TfR1直系同源物，并确定了这些直系同源物与人类TfR1之间的关键共性，这些共性是这些病毒有效传播给人类所必需的。
