Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA, USA.
Curr Opin Microbiol. 2011 Aug;14(4):476-82. doi: 10.1016/j.mib.2011.07.014. Epub 2011 Jul 30.
At least five New World arenaviruses cause severe human hemorrhagic fevers. These viruses are transmitted to humans through contact with their respective South American rodent hosts. Each uses human transferrin receptor 1 (TfR1) as its obligate receptor. Accidental similarities between human TfR1 and TfR1 orthologs of arenaviral host species enable zoonoses, whereas mice and rats are not infectable because they lack these TfR1 determinants of infection. All pathogenic New World arenaviruses bind to a common region of the apical domain of TfR1. The ability of a New World arenavirus to use human TfR1 is absolutely predictive of its ability to cause hemorrhagic fevers in humans. Nonpathogenic arenaviruses, closely related to hemorrhagic fever arenaviruses, cannot utilize human TfR1 but efficiently enter cells through TfR1 orthologs of their native rodent hosts. Mutagenesis studies suggest that minor changes in the entry glycoproteins of these nonpathogenic viruses may allow human transmission. TfR1 is upregulated as a result of iron sequestration during the acute-phase response to infection, and the severity of disease may result from amplification of viral replication during this response.
至少有五种新世界沙粒病毒会导致人类严重的出血性发热。这些病毒通过与各自的南美洲啮齿动物宿主接触传播给人类。每种病毒都使用人类转铁蛋白受体 1（TfR1）作为其必需受体。人类 TfR1 与沙粒病毒宿主物种的 TfR1 同源物之间意外的相似性导致了人畜共患病，而老鼠和大鼠则不能感染，因为它们缺乏这些感染 TfR1 的决定因素。所有致病性新世界沙粒病毒都结合到 TfR1 的顶端结构域的一个共同区域。一种新世界沙粒病毒使用人类 TfR1 的能力绝对可以预测其在人类中引起出血性发热的能力。与出血性发热沙粒病毒密切相关的非致病性沙粒病毒不能利用人类 TfR1，但可以通过其天然啮齿动物宿主的 TfR1 同源物有效地进入细胞。诱变研究表明，这些非致病性病毒的进入糖蛋白发生微小变化可能允许人类传播。由于感染急性期铁螯合作用，TfR1 上调，疾病的严重程度可能是由于在这种反应中病毒复制的放大所致。
