Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist

Genome Biology

Yusang Xie¹  Jieming Qu¹  Dong Wei²  Xinxin Zhang²  Zhao Zha³  Hong Mei³  Wei Wang³  Jia Liu⁴  Yuege Huang⁵  Wenping Li⁵ 

[1] Department of Respiratory and Critical Care Medicine, Ruijin Hospital and Institutes of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, 200025, Shanghai, China;Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 200025, Shanghai, China;Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, People’s Republic of China;Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, People’s Republic of China;Shanghai Clinical Research and Trial Center, 201210, Shanghai, People’s Republic of China;State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 510182, Guangzhou, Guangdong Province, China;Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, People’s Republic of China;Guangzhou Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou Interntional Bio Island, 510005, Guangzhou, Guangdong Province, China;Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, People’s Republic of China;University of Chinese Academy of Science, 100049, Beijing, People’s Republic of China;

关键词: CRISPR;    Genome-wide screen;    Surfaceome screen;    Rhinovirus;    OLFML3;   

DOI  :  10.1186/s13059-021-02513-w

来源: Springer

【 摘 要 】

BackgroundRhinoviruses (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.ResultsHerein, 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.ConclusionOur 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.

【 授权许可】

CC BY