SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation.
10.1007/s13238-022-00905-7
- Author:
Yichen LI
1
;
Shuaiyao LU
2
;
Jinge GU
3
;
Wencheng XIA
3
;
Shengnan ZHANG
3
;
Shenqing ZHANG
1
;
Yan WANG
4
;
Chong ZHANG
4
;
Yunpeng SUN
3
;
Jian LEI
4
;
Cong LIU
3
;
Zhaoming SU
5
;
Juntao YANG
6
;
Xiaozhong PENG
7
;
Dan LI
8
Author Information
1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200030, China.
2. National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650031, China.
3. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201210, China.
4. State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.
5. State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China. zsu@scu.edu.cn.
6. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China. yangjt@pumc.edu.cn.
7. National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650031, China. pengxiaozhong@pumc.edu.cn.
8. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200030, China. lidan2017@sjtu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
SARS-CoV-2;
nucleocapsid protein;
stress granule
- MeSH:
Amyloidogenic Proteins/metabolism*;
Amyotrophic Lateral Sclerosis/genetics*;
Animals;
COVID-19;
Cytoplasmic Granules/metabolism*;
Mammals;
SARS-CoV-2;
Stress Granules
- From:
Protein & Cell
2022;13(8):602-614
- CountryChina
- Language:English
-
Abstract:
The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
