The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage,Emerging Microbes & Infections

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The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage
Emerging Microbes & Infections ( IF 8.4 ) Pub Date : 2022-08-31 , DOI: 10.1080/22221751.2022.2111977
Ronghui Liang ₁ , Zi-Wei Ye ₁ , Chon Phin Ong ₂ , Zhenzhi Qin ₁ , Yubin Xie ₁ , Yilan Fan ₂ , Kaiming Tang ₁ , Vincent Kwok-Man Poon _{1,

3} , Chris Chung-Sing Chan _{1,

3} , Xiaomeng Yang ₁ , Hehe Cao ₁ , Kun Wang ₁ , Haoran Sun ₄ , Bodan Hu ₁ , Jian-Piao Cai ₁ , Cuiting Luo ₁ , Kenn Ka-Heng Chik _{1,

4} , Hin Chu _{1,

3,

4} , Yi Zheng ₅ , Kwok-Yung Yuen _{1,

3,

4,

6,

7,

8} , Jasper Fuk-Woo Chan _{1,

3,

4,

6,

7,

8} , Dong-Yan Jin _{2,

3,

8} , Shuofeng Yuan _{1,

3,

4}

Affiliation

State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Shatin, Hong Kong Special Administrative Region, People's Republic of China.
Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China.
Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, People's Republic of China.
Guangzhou Laboratory, Guangdong Province, People's Republic of China.

ABSTRACT

The replication and pathogenicity of SARS-CoV-2 Omicron BA.2 are comparable to that of BA.1 in experimental animal models. However, BA.2 has rapidly emerged to overtake BA.1 to become the predominant circulating SARS-CoV-2 variant worldwide. Here, we compared the replication fitness of BA.1 and BA.2 in cell culture and in the Syrian hamster model of COVID-19. Using a reverse genetics approach, we found that the BA.1-specific spike mutation G496S compromises its replication fitness, which may contribute to BA.1 being outcompeted by BA.2 in the real world. Additionally, the BA.1-unique G496S substitution confers differentiated sensitivity to therapeutic monoclonal antibodies, which partially recapitulates the immunoevasive phenotype of BA.1 and BA.2. In summary, our study identified G496S as an important determinant during the evolutionary trajectory of SARS-CoV-2.

中文翻译：

刺突受体结合基序 G496S 替代决定了 SARS-CoV-2 Omicron 亚系的复制适应性

摘要

SARS-CoV-2 Omicron BA.2 在实验动物模型中的复制和致病性与 BA.1 相当。然而，BA.2 已迅速超越 BA.1，成为全球主要的循环 SARS-CoV-2 变体。在这里，我们比较了 BA.1 和 BA.2 在细胞培养和 COVID-19 叙利亚仓鼠模型中的复制适应性。使用反向遗传学方法，我们发现 BA.1 特异性尖峰突变 G496S 会损害其复制适应性，这可能导致 BA.1 在现实世界中被 BA.2 超越。此外，BA.1 独特的 G496S 替代赋予治疗性单克隆抗体不同的敏感性，这部分概括了 BA.1 和 BA.2 的免疫逃避表型。总之，

更新日期：2022-09-01

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