Viruses have evolved intricate mechanisms to gain entry into the host cell. Identification of host proteins that serve as viral receptors has enabled insights into virus particle internalization, host and tissue tropism, and viral pathogenesis. In this review we discuss the most commonly employed methods for virus receptor discovery, specifically highlighting the use of forward genetic screens in human haploid cells. The ability to generate true knockout alleles at high saturation provides a sensitive means to study virus-host interactions. To illustrate the power of such haploid genetic screens, we highlight the discovery of the lysosomal proteins NPC1 and LAMP1 as intracellular receptors for Ebola virus and Lassa virus, respectively. From these studies emerges the notion that receptor usage by these viruses is highly dynamic, involving a programmed switch from cell surface receptor to intracellular receptor. Broad application of genetic knockout approaches will chart functional landscapes of receptors and endocytic pathways hijacked by viruses.

中文翻译：

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使用单倍体细胞寻找病毒受体。

病毒已经进化出复杂的机制来进入宿主细胞。鉴定充当病毒受体的宿主蛋白已使人们能够深入了解病毒颗粒的内在化，宿主和组织的向性性以及病毒的发病机理。在这篇综述中，我们讨论了最常使用的病毒受体发现方法，特别强调了在人类单倍体细胞中使用正向遗传筛选。在高饱和度下产生真正的敲除等位基因的能力为研究病毒与宿主之间的相互作用提供了一种灵敏的手段。为了说明这种单倍体遗传筛选的功能，我们重点介绍了溶酶体蛋白NPC1和LAMP1分别作为埃博拉病毒和拉沙病毒的细胞内受体的发现。这些研究表明，这些病毒对受体的使用是高度动态的，涉及从细胞表面受体到细胞内受体的程序性转换。基因敲除方法的广泛应用将绘制病毒劫持的受体和内吞途径的功能分布图。