小柯机器人

美国加州大学旧金山分校Jonathan S. Weissman与Marco Y. Hein合作揭示人类巨细胞病毒感染的功能性单细胞基因组学。该研究于2021年10月25日在线发表于国际一流学术期刊《自然—生物技术》。

通过汇集的CRISPR干扰和核酸酶筛选，研究人员确定了参与人类巨细胞病毒感染的每个病毒和宿主因子的功能贡献。为了确定关键宿主和病毒因子的遗传扰动如何改变感染的时间、过程和进展，研究人员应用Perturb-seq记录了数万个CRISPR修饰的单细胞转录组，并发现通常情况下，大多数细胞遵循一个定型的转录轨迹。扰乱关键的宿主因子并不改变立体的转录轨迹本身，但可以阻滞、延迟或加速沿着轨迹的进展，使人们能够确定宿主因子发挥作用的感染阶段。相反，对病毒因素的扰动可以产生不同的、中止性的轨迹。

这些结果揭示了宿主和病毒因素的作用，并为剖析宿主-病原体的相互作用提供了一个路线图。

据介绍，了解病毒和宿主因素如何相互作用以及扰动如何影响感染是设计抗病毒干预措施的基础。

附：英文原文

Title: Functional single-cell genomics of human cytomegalovirus infection

Author: Hein, Marco Y., Weissman, Jonathan S.

Issue&Volume: 2021-10-25

Abstract: Understanding how viral and host factors interact and how perturbations impact infection is the basis for designing antiviral interventions. Here we define the functional contribution of each viral and host factor involved in human cytomegalovirus infection in primary human fibroblasts through pooled CRISPR interference and nuclease screening. To determine how genetic perturbation of critical host and viral factors alters the timing, course and progression of infection, we applied Perturb-seq to record the transcriptomes of tens of thousands of CRISPR-modified single cells and found that, normally, most cells follow a stereotypical transcriptional trajectory. Perturbing critical host factors does not change the stereotypical transcriptional trajectory per se but can stall, delay or accelerate progression along the trajectory, allowing one to pinpoint the stage of infection at which host factors act. Conversely, perturbation of viral factors can create distinct, abortive trajectories. Our results reveal the roles of host and viral factors and provide a roadmap for the dissection of host–pathogen interactions. Pooled and single-cell CRISPR screens provide a detailed map of human cytomegalovirus infection.

DOI: 10.1038/s41587-021-01059-3

Source: https://www.nature.com/articles/s41587-021-01059-3

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex