Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents
Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents
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DOI：
10.1038/s41586-022-05482-7
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发表时间：
2022-11-02
期刊：
影响因子：
64.8
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
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作者：
Uraki, Ryuta;Halfmann, Peter J.;Kawaoka, Yoshihiro
SARS-CoV-2 Omicron变种的BA.2亚型已经在世界上大多数国家占据主导地位；然而，BA.4和BA.5的流行率在几个地区迅速增加。BA.2在动物模型中的致病性低于以前流行的关注变种(1-4)。然而，与BA.2相比，BA.4和BA.5在刺突蛋白中具有额外的替换，这在病毒进入过程中起着关键作用，这引起了人们对BA.4和BA.5的复制能力和致病力高于BA.2的担忧。在这里，我们评估了BA.4和BA.5分离株在叙利亚野生型仓鼠、人ACE2(HACE2)转基因仓鼠和hACE2转基因小鼠身上的复制能力和致病性。在啮齿动物模型中，我们没有观察到BA.2、BA.4和BA.5分离株在生长能力或致病性方面的明显差异，并且与先前流行的Delta(B.1.617.2谱系)分离株相比，致病性较低。此外，活体竞争实验显示，BA.5在仓鼠中的竞争能力强于BA.2，而BA.4和BA.2表现出类似的适应性。这些结果表明，BA.4和BA.5临床分离株对啮齿动物的致病性与BA.2相似，BA.5的病毒适合性优于BA.2。
The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern(1-4). Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here we have evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters and hACE2 transgenic mice. We have observed no obvious differences among BA.2, BA.4 and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2.