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

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...

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Detalles Bibliográficos
Autores principales: Li, Yichen, Lu, Shuaiyao, Gu, Jinge, Xia, Wencheng, Zhang, Shengnan, Zhang, Shenqing, Wang, Yan, Zhang, Chong, Sun, Yunpeng, Lei, Jian, Liu, Cong, Su, Zhaoming, Yang, Juntao, Peng, Xiaozhong, Li, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Higher Education Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983322/
https://www.ncbi.nlm.nih.gov/pubmed/35384603
http://dx.doi.org/10.1007/s13238-022-00905-7
Descripción
Sumario: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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13238-022-00905-7.