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.
Keywords: SARS-CoV-2; nucleocapsid protein; stress granule.
【저자키워드】 SARS-CoV-2, nucleocapsid protein, stress granule., 【초록키워드】 ACE2, Mutation, Stress, SARS-COV-2 infection, Infection, Proteins, in vitro, nucleocapsid protein, Protein, cells, nucleocapsid, N protein, experiment, stress granule, stress granules, interactions, neurodegeneration, non-specific, NMR, cellular, Invasion, host cells, phase transition, increased risk, scenario, incorporation, aggregation, mammalian cells, clearance, mammalian cell, infect, Host, Cell, bind, stimulated, reported, addition, indicate, occur, promote, impair, FUS, 【제목키워드】 stress granule, promote, impair,