RESEARCH ARTICLE

SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation

  • Yichen Li 1,2 ,
  • Shuaiyao Lu 3,4 ,
  • Jinge Gu 6,7 ,
  • Wencheng Xia 6,7 ,
  • Shengnan Zhang 6,7 ,
  • Shenqing Zhang 1,2 ,
  • Yan Wang 8 ,
  • Chong Zhang 8 ,
  • Yunpeng Sun 6,7 ,
  • Jian Lei 8 ,
  • Cong Liu 6,7 ,
  • Zhaoming Su , 8 ,
  • Juntao Yang , 5 ,
  • Xiaozhong Peng , 3,4 ,
  • Dan Li , 1,9,10
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  • 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. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China
  • 3. 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
  • 4. State Key Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
  • 5. 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
  • 6. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China
  • 7. University of Chinese Academy of Sciences, Beijing 100049, China
  • 8. State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China
  • 9. Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
  • 10. Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China

Received date: 25 Nov 2021

Accepted date: 27 Dec 2021

Published date: 15 Aug 2022

Copyright

2022 The Author(s)

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.

Cite this article

Yichen Li , Shuaiyao Lu , Jinge Gu , Wencheng Xia , Shengnan Zhang , Shenqing Zhang , Yan Wang , Chong Zhang , Yunpeng Sun , Jian Lei , Cong Liu , Zhaoming Su , Juntao Yang , Xiaozhong Peng , Dan Li . SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation[J]. Protein & Cell, 2022 , 13(8) : 602 -614 . DOI: 10.1007/s13238-022-00905-7

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