| Autor: |
Li, Zhean, Luo, Lingling, Ju, Xiaohui, Huang, Shisheng, Lei, Liqun, Yu, Yanying, Liu, Jia, Zhang, Pumin, Chi, Tian, Ma, Peixiang, Huang, Cheng, Huang, Xingxu, Ding, Qiang, Zhang, Yu |
| Zdroj: |
EMBO Journal; Dec2024, Vol. 43 Issue 24, p6444-6468, 25p |
| Abstrakt: |
Host cell-encoded deaminases act as antiviral restriction factors to impair viral replication and production through introducing mutations in the viral genome. We sought to understand whether deaminases are involved in SARS-CoV-2 mutation and replication, and how the viral factors interact with deaminases to trigger these processes. Here, we show that APOBEC and ADAR deaminases act as the driving forces for SARS-CoV-2 mutagenesis, thereby blocking viral infection and production. Mechanistically, SARS-CoV-2 nucleocapsid (N) protein, which is responsible for packaging viral genomic RNA, interacts with host deaminases and co-localizes with them at stress granules to facilitate viral RNA mutagenesis. N proteins from several coronaviruses interact with host deaminases at RNA granules in a manner dependent on its F17 residue, suggesting a conserved role in modulation of viral mutagenesis in other coronaviruses. Furthermore, mutant N protein bearing a F17A substitution cannot localize to deaminase-containing RNA granules and leads to reduced mutagenesis of viral RNA, providing support for its function in enhancing deaminase-dependent viral RNA editing. Our study thus provides further insight into virus-host cell interactions mediating SARS-CoV-2 evolution. Synopsis: Host cell-encoded deaminases act as innate restriction factors that enhance viral genome mutation and evolution. This study shows that SARS-CoV-2 nucleocapsid (N) protein interacts with host deaminases at RNA granules, thus promoting viral mutagenesis. N protein specifically interacts with host ADAR and APOBEC deaminases. N protein localises to deaminase-containing RNA granules via RNA-dependent phase separation. N protein promotes deaminase-induced RNA editing of SARS-CoV-2 genome. N protein with a F17A mutation fails to localise to deaminase-containing RNA granules and reduces host deaminase-dependent mutagenesis of SARS-CoV-2 genome. Coronaviral N protein interacts and co-condensates with host ADAR and APOBEC deaminases to promote viral RNA editing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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