The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS)1,2. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)3–6 as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1—a member of the cadherin superfamily7,8—to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses.New World hantaviruses—which cause a severe human respiratory disease—use surface glycoproteins to bind to the human protocadherin-1 protein and enter endothelial cells in vitro; depleting protocadherin-1 in Syrian golden hamsters largely protects against disease.

中文翻译：

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Protocadherin-1 对于新世界汉坦病毒进入细胞至关重要

汉坦病毒从啮齿动物宿主向北美和南美人类的人畜共患病传播与严重且经常致命的呼吸道疾病汉坦病毒肺综合征 (HPS)1,2 相关。没有针对 HPS 的特定抗病毒治疗可用，也没有已知的体内对汉坦病毒感染和 HPS 易感性的分子决定因素。在这里，我们将人类哮喘相关基因 protocadherin-1 (PCDH1)3-6 鉴定为导致 HPS、安第斯病毒 (ANDV) 和 Sin Nombre 病毒 (SNV) 的两种汉坦病毒进入和感染肺内皮细胞的重要决定因素。在体外，我们表明 ANDV 和 SNV 的表面糖蛋白直接识别 PCDH1 的最外层细胞外重复结构域（钙粘蛋白超家族的成员 7,8）以利用 PCDH1 进入。体内，PCDH1 的基因消融使叙利亚金仓鼠对通常致命的 ANDV 攻击具有高度抵抗力。靶向 PCDH1 可以提供减少由新世界汉坦病毒引起的感染和疾病的策略。新世界汉坦病毒——导致严重的人类呼吸道疾病——使用表面糖蛋白与人原钙粘蛋白-1 蛋白结合并在体外进入内皮细胞；在叙利亚金仓鼠中消耗 protocadherin-1 在很大程度上可以预防疾病。