tetano
Editor, Senior Moderator
EMBO J
. 2024 Nov 20.
doi: 10.1038/s44318-024-00314-y. Online ahead of print. Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis
Zhean Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Lingling Luo[SUP] #[/SUP][SUP] 3 4 [/SUP], Xiaohui Ju[SUP] #[/SUP][SUP] 5 [/SUP], Shisheng Huang[SUP] #[/SUP][SUP] 6 [/SUP], Liqun Lei[SUP] 1 [/SUP], Yanying Yu[SUP] 5 [/SUP], Jia Liu[SUP] 7 [/SUP], Pumin Zhang[SUP] 1 [/SUP], Tian Chi[SUP] 6 [/SUP], Peixiang Ma[SUP] 8 9 [/SUP], Cheng Huang[SUP] 10 [/SUP], Xingxu Huang[SUP] 11 12 [/SUP], Qiang Ding[SUP] 13 [/SUP], Yu Zhang[SUP] 14 15 [/SUP]
Affiliations
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.
Keywords: Deaminases; Innate Immunity; Mutagenesis; SARS-CoV-2.
. 2024 Nov 20.
doi: 10.1038/s44318-024-00314-y. Online ahead of print. Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis
Zhean Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Lingling Luo[SUP] #[/SUP][SUP] 3 4 [/SUP], Xiaohui Ju[SUP] #[/SUP][SUP] 5 [/SUP], Shisheng Huang[SUP] #[/SUP][SUP] 6 [/SUP], Liqun Lei[SUP] 1 [/SUP], Yanying Yu[SUP] 5 [/SUP], Jia Liu[SUP] 7 [/SUP], Pumin Zhang[SUP] 1 [/SUP], Tian Chi[SUP] 6 [/SUP], Peixiang Ma[SUP] 8 9 [/SUP], Cheng Huang[SUP] 10 [/SUP], Xingxu Huang[SUP] 11 12 [/SUP], Qiang Ding[SUP] 13 [/SUP], Yu Zhang[SUP] 14 15 [/SUP]
Affiliations
- PMID: 39567830
- DOI: 10.1038/s44318-024-00314-y
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.
Keywords: Deaminases; Innate Immunity; Mutagenesis; SARS-CoV-2.