Nucleocapsid mutations R203K/G204R increase the infectivity, fitness, and virulence of SARS-CoV-2

被引：137

作者：

Wu, Haibo ^{[1
]}

Xing, Na ^{[2
]}

Meng, Kaiwen ^{[3
]}

Fu, Beibei ^{[1
]}

Xue, Weiwei ^{[4
]}

Dong, Pan ^{[1
]}

Tang, Wanyan ^{[5
]}

Xiao, Yang ^{[1
]}

Liu, Gexin ^{[1
]}

Luo, Haitao ^{[1
]}

Zhu, Wenzhuang ^{[3
]}

Lin, Xiaoyuan ^{[1
]}

Meng, Geng ^{[3
]}

Zhu, Zhenglin ^{[1
]}

机构：

[1] Chongqing Univ, Sch Life Sci, 55 Daxuecheng South Rd, Chongqing 401331, Peoples R China

[2] Free Univ Berlin, Inst Virol, Robert Von Ostertag Str 7-13, D-14163 Berlin, Germany

[3] China Agr Univ, Coll Vet Med, 2 Yuanmingyuan West Rd, Beijing 100094, Peoples R China

[4] Chongqing Univ, Sch Pharmaceut Sci, 55 Daxuecheng South Rd, Chongqing 401331, Peoples R China

[5] Chongqing Univ, Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis &, 181 Hanyu Rd, Chongqing 400030, Peoples R China

来源：

CELL HOST & MICROBE | 2021年 / 29卷 / 12期

基金：

中国国家自然科学基金;

关键词：

TRANSMISSION; FRAMEWORK; SELECTION; DISCOVERY; PATTERNS; LINKAGE;

D O I：

10.1016/j.chom.2021.11.005

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Previous work found that the co-occurring mutations R203K/G204R on the SARS-CoV-2 nucleocapsid (N) protein are increasing in frequency among emerging variants of concern or interest. Through a combination of in silico analyses, this study demonstrates that R203K/G204R are adaptive, while large-scale phylogenetic analyses indicate that R203K/G204R associate with the emergence of the high-transmissibility SARS-CoV-2 lineage B.1.1.7. Competition experiments suggest that the 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly related to ribonucleocapsid (RNP) assembly. Moreover, the 203K/204R virus shows increased infectivity in human lung cells and hamsters. Accordingly, we observe a positive association between increased COVID-19 severity and sample frequency of 203K/204R. Our work suggests that the 203K/204R mutations contribute to the increased transmission and virulence of select SARS-CoV-2 variants. In addition to mutations in the spike protein, mutations in the nucleocapsid protein are important for viral spreading during the pandemic.

引用

页码：1788 / +

页数：21

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