期刊
BIOLOGY DIRECT
卷 16, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13062-021-00305-7
关键词
SARS-COV-2; COVID-19; Syncytia; Cell fusion; Micronuclei; DNA damage signaling; gamma H2Ax; cGAS
类别
资金
- Key Science & Technology Project of Beijing Educational Committee
- Beijing Municipal Natural Science Foundation [KZ202110025029]
- Beijing Municipal Administration of Hospitals Incubating Program [PX2021033]
Research showed that SARS-CoV-2 infection could lead to the formation of micronuclei within cells, activating DNA damage response and cGAS-STING signaling, providing insights into the pathological effects of the infection and potential targets for COVID-19 therapy.
SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS-STING signaling, as indicated by micronucleus translocation of gamma H2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.
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