Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis

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.

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Publication Details

Journal
The EMBO Journal
Published
2024-11-20
DOI
https://doi.org/10.1038/s44318-024-00314-y
Citations
5
Primary Topic
RNA regulation and disease
Type
article
Field-Weighted Citation Impact
1.17

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article

Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis

Xiaohui Ju, Peixiang Ma, Yanying Yu, Liqun Lei et al.
5 citations
The EMBO Journal
RNA regulation and disease
1.17
article

Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis

Xiaohui Ju, Peixiang Ma, Yanying Yu, Liqun Lei, Zhean Li, Lingling Luo, Pumin Zhang, Xingxu Huang, Shisheng Huang, Qiang Ding, Jia Liu, Yu Zhang, Tian Chi, Cheng Huang
article en
5 citations

Abstract

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.

The EMBO JournalVol. 43(24)
Shanghai Jiao Tong University (CN), Sir Run Run Shaw Hospital (CN), ShanghaiTech University (CN), Guangzhou Experimental Station (CN), Shanghai Ninth People's Hospital (CN), Shanghai University of Traditional Chinese Medicine (CN), Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine (CN), First Affiliated Hospital Zhejiang University (CN), Zhejiang University (CN), Tsinghua University (CN)
National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Tsinghua University, ShanghaiTech University, Beijing Municipal Natural Science Foundation, National Key Research and Development Program of China
Good health and well-being
Openalex Percentile: Top 21%
RNA regulation and disease
1.17
DOIOpen Access PDFOpenAlex
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