Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, People's Republic of China.
Department of Respiratory and Critical Care Medicine, Ruijin Hospital and Institutes of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
Genome Biol. 2021 Oct 22;22(1):297. doi: 10.1186/s13059-021-02513-w.
Rhinoviruses (RVs) cause more than half of common colds and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which have proven clinical relevance.
Herein, we systematically compare genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome screen outperforms the genome-wide screen in the success rate of hit identification. Importantly, using the surfaceome screen, we identify olfactomedin-like 3 (OLFML3) as a novel host factor of RV serotypes A and B, including a clinical isolate. We find that OLFML3 is a RV-inducible suppressor of the innate immune response and that OLFML3 antagonizes type I interferon (IFN) signaling in a SOCS3-dependent manner.
Our study suggests that RV-induced OLFML3 expression is an important mechanism for RV to hijack the immune system and underscores surfaceome CRISPR screen in identifying viral host factors.
鼻病毒（RV）导致超过一半的普通感冒，在某些情况下还会导致更严重的疾病。使用 siRNA 或全基因组 CRISPR 筛选对 RV 的功能基因组学分析揭示了一组有限的宿主因子，其中很少有具有临床相关性。
在此，我们系统地比较了全基因组 CRISPR 筛选和表面蛋白靶向 CRISPR 筛选（称为表面组 CRISPR 筛选），以评估它们在鉴定 RV 宿主因子方面的效率。我们发现表面组筛选在命中鉴定的成功率方面优于全基因组筛选。重要的是，使用表面组筛选，我们确定嗅觉素样 3（OLFML3）是 RV 血清型 A 和 B 的新型宿主因子，包括临床分离株。我们发现 OLFML3 是 RV 诱导的先天免疫反应抑制剂，并且 OLFML3 以 SOCS3 依赖的方式拮抗 I 型干扰素（IFN）信号传导。
我们的研究表明，RV 诱导的 OLFML3 表达是 RV 劫持免疫系统的重要机制，并强调了表面组 CRISPR 筛选在鉴定病毒宿主因子方面的作用。
