The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling.
The viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference....
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012886 |
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| author | Yongkui Li Moran Li Heng Xiao Feng Liao Miaomiao Shen Weiwei Ge Junxian Ou Yuqing Liu Lumiao Chen Yue Zhao Pin Wan Jinbiao Liu Jun Chen Xianwu Lan Shaorong Wu Qiang Ding Geng Li Qiwei Zhang Pan Pan |
| author_facet | Yongkui Li Moran Li Heng Xiao Feng Liao Miaomiao Shen Weiwei Ge Junxian Ou Yuqing Liu Lumiao Chen Yue Zhao Pin Wan Jinbiao Liu Jun Chen Xianwu Lan Shaorong Wu Qiang Ding Geng Li Qiwei Zhang Pan Pan |
| author_sort | Yongkui Li |
| collection | DOAJ |
| description | The viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference. However, its biological function in viral evolution is not well understood. SARS-CoV-2 N protein mutations were analyzed in Delta, Omicron, and original strains. Two mutations with a methionine (M) residue at site 203 and a tyrosine (Y) residue at site 377 of the N protein were found in Delta strain but not in Omicron and original strains, and promoted SARS-CoV-2 infection therein. Those mutations, R203M and D377Y, enhanced the inhibitory impact of N protein on the impairment of RIG-I-mediated antiviral signaling, such as IRF3 phosphorylation and IFN-β activation. The viral RNA-binding activity of N protein was promoted by these mutations, effectively attenuating the recognition and interaction of RIG-I with viral RNA compared to the original or other variants. The R203M/D377Y mutations thus enhanced the suppressive activity of the N protein on RIG-I-mediated interferon induction both in vitro and in vivo, which in turn promoted viral replication. This study helps to understand the variability of SARS-CoV-2 in regulating host immunity. |
| format | Article |
| id | doaj-art-b3497fcddf7c4432995d04fe7b0ea2de |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-b3497fcddf7c4432995d04fe7b0ea2de2025-02-05T05:30:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101288610.1371/journal.ppat.1012886The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling.Yongkui LiMoran LiHeng XiaoFeng LiaoMiaomiao ShenWeiwei GeJunxian OuYuqing LiuLumiao ChenYue ZhaoPin WanJinbiao LiuJun ChenXianwu LanShaorong WuQiang DingGeng LiQiwei ZhangPan PanThe viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference. However, its biological function in viral evolution is not well understood. SARS-CoV-2 N protein mutations were analyzed in Delta, Omicron, and original strains. Two mutations with a methionine (M) residue at site 203 and a tyrosine (Y) residue at site 377 of the N protein were found in Delta strain but not in Omicron and original strains, and promoted SARS-CoV-2 infection therein. Those mutations, R203M and D377Y, enhanced the inhibitory impact of N protein on the impairment of RIG-I-mediated antiviral signaling, such as IRF3 phosphorylation and IFN-β activation. The viral RNA-binding activity of N protein was promoted by these mutations, effectively attenuating the recognition and interaction of RIG-I with viral RNA compared to the original or other variants. The R203M/D377Y mutations thus enhanced the suppressive activity of the N protein on RIG-I-mediated interferon induction both in vitro and in vivo, which in turn promoted viral replication. This study helps to understand the variability of SARS-CoV-2 in regulating host immunity.https://doi.org/10.1371/journal.ppat.1012886 |
| spellingShingle | Yongkui Li Moran Li Heng Xiao Feng Liao Miaomiao Shen Weiwei Ge Junxian Ou Yuqing Liu Lumiao Chen Yue Zhao Pin Wan Jinbiao Liu Jun Chen Xianwu Lan Shaorong Wu Qiang Ding Geng Li Qiwei Zhang Pan Pan The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling. PLoS Pathogens |
| title | The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling. |
| title_full | The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling. |
| title_fullStr | The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling. |
| title_full_unstemmed | The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling. |
| title_short | The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling. |
| title_sort | r203m and d377y mutations of the nucleocapsid protein promote sars cov 2 infectivity by impairing rig i mediated antiviral signaling |
| url | https://doi.org/10.1371/journal.ppat.1012886 |
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