Identification of factors involved in dsRNA-induced cell death by CRISPR-Cas9 screen

When facing a viral infection, the organism has to put in place a number of defense mechanisms in order to clear the pathogen from the cell. At the early phase of this preparation for fighting against the invader, the innate immune response is triggered by the sensing of danger signals. Among those molecular cues, double-stranded (dsRNA) is a very potent inducer of different reactions at the cellular level that can ultimately lead to cell death. Using a genome-wide screening approach, we set to identify genes involved in dsRNA entry, sensing and apoptosis induction in human cells. This allowed us to determine that the heparan sulfate pathway and the Conserved Oligomeric Golgi complex are key determinants allowing entry of both dsRNA and viral nucleic acid leading to cell death.

当机体遭遇病毒感染时，需启动一系列防御机制以清除细胞内的病原体。在启动抗病毒免疫防御的早期阶段，天然免疫应答通过感知危险信号而被激活。在这些分子信号中，双链核糖核酸（double-stranded RNA, dsRNA）是一种强效诱导细胞层面发生多种反应的分子，最终可引发细胞死亡。本研究采用全基因组筛选策略，旨在鉴定人类细胞中参与dsRNA摄取、感知以及细胞凋亡诱导的基因。通过该研究，我们确定硫酸乙酰肝素通路（heparan sulfate pathway）与保守寡聚高尔基体复合体（Conserved Oligomeric Golgi complex）是介导dsRNA与病毒核酸摄取并最终引发细胞死亡的关键决定因素。