DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication

doi:10.1101/2025.02.04.636569

KMS > 免疫化学研究所

	DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication
	Feng, Fei 1; Chen, Jiannan 1,3; Li, Rong2 ; Zhu, Yunkai 1; Ma, Yanlong 1; Wang, Ziqiao 1; Wang, Yuyan 1; Gao, Zhichao 1; Yang, Lulu 1; Yu, Yin 1; Liu, Yanfeng 5; Sun, Yingjie ; Liao, Ying 5; Huang, Xinxin 6; Zhang, Qisheng 12; Huang, Yongheng 12; Qiu, Lin 13; Wu, Jiayu 13; Zhao, Jingxian 10; Liu, Chao 3; Ding, Qiang 7; Xie, Youhua 1; Yuan, Zhenghong 1; Hong, Yue 4; Zhang, Ping 3; Sun, Jing 8; Zhao, Jincun2,8,9,10,11 ; Zhang, Rong 1
	2025-02-07
状态	已发表
摘要	The SARS-CoV-2 pandemic and the emergence of novel variants underscore the need to understand host-virus interactions and identify host factors that restrict viral infection. Here, we perform a genome-wide CRISPR knockout screen to identify host restriction factors for SARS-CoV-2, revealing DAZAP2 as a potent antiviral gene. DAZAP2, previously implicated in SARS-CoV-2 restriction, is found to inhibit viral entry by blocking virion fusion with both endolysosomal and plasma membranes. Additionally, DAZAP2 suppresses genomic RNA replication without affecting the primary translation of viral replicases. We demonstrate that DAZAP2 functions as a pan-coronavirus restriction factor across four genera of coronaviruses. Importantly, knockout of DAZAP2 enhances SARS-CoV-2 infection in mouse models and in human primary airway epithelial cells, confirming its physiological relevance. Mechanistically, antiviral activity of DAZAP2 appears to be indirect, potentially through the regulation of host gene expression, as it primarily localizes to the nucleus. Our findings provide new insights into the host defense system against coronaviruses and highlight DAZAP2 as a potential target for host-directed antiviral therapies.
语种	英语
DOI	10.1101/2025.02.04.636569
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:121184051
WOS类目	Microbiology
资助项目	National Natural Science Foundation of China["32270163","32041005","82341084","81971500","92169110"] ; National Key Research and Development Program of China["2024YFC2607300","2020YFA0707701"] ; Program of Shanghai Academic/Technology Research Leader[22XD1420600] ; Shanghai Municipal Science and Technology Major Project[ZD2021CY001] ; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences[2023-PT310-02] ; Shenzhen Medical Research Fund (SMRF)[B2302029] ; Natural Science Foundation of Shanghai[19ZR1470400]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/507020
专题	免疫化学研究所生命科学与技术学院_博士生免疫化学研究所_特聘教授组_赵金存组
通讯作者	Hong, Yue; Zhang, Ping; Sun, Jing; Zhao, Jincun; Zhang, Rong
作者单位	1.Fudan Univ, Shanghai Frontiers Sci Ctr Pathogen Microorganisms & Infect, Key Lab Med Mol Virol MOE NHC CAMS, Shanghai Inst Infect Dis,Sch Basic Med Sci,Shanghai Med Coll, Shanghai 200032, Peoples R China 2.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Sun Yat sen Univ, Zhongshan Sch Med, Dept Immunol & Microbiol, Guangzhou 510080, Peoples R China 4.Hainan Univ, Sch Life & Hlth Sci, Haikou 570228, Peoples R China 5.CAAS, Shanghai Vet Res Inst, Shanghai 200241, Peoples R China 6.Tech Ctr Anim Plant & Food Inspection & Quarantine Shanghai Customs, Shanghai 200032, Peoples R China 7.Tsinghua Univ, Ctr Infect Dis Res, Sch Med, Beijing 100086, Peoples R China 8.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, State Key Lab Resp Dis, Natl Clin Res Ctr Resp Dis,Affiliated Hosp 1, Guangzhou 510182, Peoples R China 9.Guangzhou Med Univ, Guangzhou Peoples Hosp 8, Inst Infect Dis, Guangzhou 510442, Peoples R China 10.Guangzhou Natl Lab, Guangzhou 510005, Peoples R China 11.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Inst Hepatol,Natl Clin Res Ctr Infect Dis,Sch Med, Shenzhen 518112, Peoples R China 12.U LAB, Porostem Biomed, Shanghai 200131, Peoples R China 13.CAS, Inst Ctr Shared Technol & Facil SINH, Shanghai 200131, Peoples R China
推荐引用方式 GB/T 7714	Feng, Fei,Chen, Jiannan,Li, Rong,et al. DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication. 2025.