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.
Emerg Microbes Infect. 2022 Dec;11(1):2093-2101. doi: 10.1080/22221751.2022.2111977.
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.
奥密克戎变异株 BA.2 在实验动物模型中的复制能力和致病力与 BA.1 相当。然而，BA.2 迅速出现并取代 BA.1，成为全球主要流行的 SARS-CoV-2 变异株。在此，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。我们通过反向遗传学方法发现，BA.1 特异性刺突突变 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 所淘汰。此外，BA.1 独特的 G496S 取代赋予了对治疗性单克隆抗体的差异化敏感性，部分再现了 BA.1 和 BA.2 的免疫逃逸表型。总之，我们的研究确定了 G496S 是 SARS-CoV-2 进化过程中的一个重要决定因素。
