Hunting Viral Receptors Using Haploid Cells.
Hunting Viral Receptors Using Haploid Cells.
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DOI：
10.1146/annurev-virology-100114-055119
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发表时间：
2015-11
影响因子：
11.3
通讯作者：
Carette JE
中科院分区：
文献类型：
--
作者：
Pillay S;Carette JE
病毒已经进化出复杂的机制来进入宿主细胞。关键受体的鉴定使人们能够深入了解病毒颗粒内化、宿主和组织趋向性以及病毒的发病机制。在这篇综述中，我们讨论了最常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敲除等位基因的能力为研究病毒与宿主的相互作用提供了一种敏感的手段。例如，单倍体遗传筛选鉴定溶酶体蛋白NPC1和LAMP1分别是埃博拉病毒和拉沙病毒的细胞内受体。从这些研究中出现了这样的概念，即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出病毒劫持的受体和内吞途径的功能图景。
Viruses have evolved intricate mechanisms to gain entry into the host cell. Identification of critical 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. As an example, haploid genetic screens identified 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.