Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains in vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responses in vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. Finally, we demonstrate that human CD300lf (huCD300lf) is not essential for HNoV infection, nor does huCD300lf inhibit binding of HNoV virus-like particles to glycans. Thus, we report huCD300lf is not a receptor for HNoV.

中文翻译：

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CD300lf 是鼠诺如病毒的主要生理受体，但不是人诺如病毒。

鼠诺如病毒（MNoV）是人类诺如病毒（HNoV）和更广泛的粘膜病毒感染的重要模型。病毒受体的利用是细胞趋向性、宿主范围和发病机制的主要决定因素。HNoV 的真正受体尚不清楚。最近，我们确定 CD300lf 是 MNoV 的蛋白质受体。有趣的是，其旁系同源物 CD300ld 也足以在体外感染 MNoV。在这里，我们探讨了 CD300lf 是否是体内唯一的生理受体，以及 HNoV 是否可以使用 CD300 直向同源物作为进入受体。我们报告 CD300ld 和 CD300lf 足以在体外感染多种 MNoV 毒株。我们进一步证明 CD300lf 对于口服和肠胃外 MNoV 感染以及在体内引发抗 MNoV 体液反应至关重要。在 STAT1 信号传导缺陷的小鼠中，MNoV 诱导的致死需要 CD300lf。最后，我们证明人CD300lf (huCD300lf)对于HNoV感染不是必需的，huCD300lf也不抑制HNoV病毒样颗粒与聚糖的结合。因此，我们报告 huCD300lf 不是 HNoV 的受体。