Discovery of a proteinaceous cellular receptor for a norovirus.
Discovery of a proteinaceous cellular receptor for a norovirus.
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DOI：
10.1126/science.aaf1220
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发表时间：
2016-08-26
期刊：
影响因子：
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通讯作者：
Virgin HW
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文献类型：
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作者：
Orchard RC;Wilen CB;Doench JG;Baldridge MT;McCune BT;Lee YC;Lee S;Pruett-Miller SM;Nelson CA;Fremont DH;Virgin HW
人类诺如病毒（NoV）是全球胃肠炎的主要原因，但对NoV感染所需的宿主因素知之甚少。我们鉴定了鼠NoV（MNoV）诱导的细胞死亡所必需的宿主分子，包括作为蛋白质受体的CD 300 lf。CD 300 lf对于细胞系和原代细胞中的MnoV结合和复制是必需的。此外，Cd 300 lf −/−小鼠对MNoV感染具有抗性。CD 300 lf在人细胞中的表达打破了限制MnoV复制的物种屏障。CD 300 lf胞外域的晶体结构揭示了由MNoV感染的关键残基组成的潜在配体结合裂缝。因此，蛋白质受体的存在是MNoV物种嗜性的主要决定因素，而NoV复制所需的细胞机制的其他组分在人和小鼠之间是保守的。
Human noroviruses (NoV) are a leading cause of gastroenteritis globally, yet host factors required for NoV infection are poorly understood. We identified host molecules essential for murine NoV (MNoV) induced cell death including CD300lf as a proteinaceous receptor. CD300lf is essential for MNoV binding and replication in cell lines and primary cells. Additionally, Cd300lf−/− mice are resistant to MNoV infection. Expression of CD300lf in human cells breaks the species barrier restricting MNoV replication. The crystal structure of the CD300lf ectodomain revealed a potential ligand binding cleft composed of residues critical for MNoV infection. Therefore, the presence of a proteinaceous receptor is the primary determinant of MNoV species tropism while other components of cellular machinery required for NoV replication are conserved between humans and mice.