SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2(ZYG)(11)(B) activity

doi:10.1083/jcb.202108015

	SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2(ZYG)(11)(B) activity
	Wang, Liying 1,4; Liu, Chao 1,4; Yang, Bo 5; Zhang, Haotian 2; Jiao, Jian 9,10; Zhang, Ruidan 4; Liu, Shujun 3; Xiao, Sai 4; Chen, Yinghong 1,4; Liu, Bo 4; Ma, Yanjie 1,4; Duan, Xuefeng 6; Guo, Yueshuai 2; Guo, Mengmeng 1,4; Wu, Bingbing 1,4; Wang, Xiangdong 9,10; Huang, Xingxu8 ; Yang, Haitao7,8 ; Gui, Yaoting 5; Fang, Min 6; Zhang, Luo 9,10; Duo, Shuguang 3; Guo, Xuejiang 2; Li, Wei 1,4
	2022-06-08
发表期刊	JOURNAL OF CELL BIOLOGY (IF:7.4[JCR-2023],8.1[5-Year])
ISSN	0021-9525
EISSN	1540-8140
卷号	221 期号:7
DOI	10.1083/jcb.202108015
摘要	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2(ZYG11B) complex by interacting with ZYG11B. Enhanced CUL2(ZYG11B) activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNEC5) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2(ZYG11B) to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.
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收录类别	SCIE
语种	英语
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000868088300001
出版者	ROCKEFELLER UNIV PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243349
专题	生命科学与技术学院_PI研究组_黄行许组免疫化学研究所_PI研究组_杨海涛组
通讯作者	Zhang, Luo; Duo, Shuguang; Guo, Xuejiang; Li, Wei
作者单位	1.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou, Guangdong, Peoples R China; 2.Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Lab Anim Ctr, Inst Zool, Beijing, Peoples R China; 4.Chinese Acad Sci, Inst Zool, Stem Cell & Regenerat Med Innovat Inst, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China; 5.Peking Univ Shenzhen Hosp, Shenzhen PKU HKUST Med Ctr, Inst Urol, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Shenzhen, Peoples R China; 6.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China; 7.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China; 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 9.Capital Med Univ, Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China; 10.Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Wang, Liying,Liu, Chao,Yang, Bo,et al. SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2(ZYG)(11)(B) activity[J]. JOURNAL OF CELL BIOLOGY,2022,221(7).
APA	Wang, Liying.,Liu, Chao.,Yang, Bo.,Zhang, Haotian.,Jiao, Jian.,...&Li, Wei.(2022).SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2(ZYG)(11)(B) activity.JOURNAL OF CELL BIOLOGY,221(7).
MLA	Wang, Liying,et al."SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2(ZYG)(11)(B) activity".JOURNAL OF CELL BIOLOGY 221.7(2022).