Here we investigated the virulence properties of a unique cell-adapted SARS-CoV-2 mutant showing a ten-amino acid deletion encompassing the furin cleavage site of the spike protein (Δ₆₈₀SPRAARSVAS₆₈₉; Δ680-689-B.1) in comparison to its parental strain (wt-B.1) and two Delta variants (AY.122 and AY.21). After IN inoculation, transgenic K18-hACE2 mice were monitored for 14 days for weight change, lethality, clinical score, and oral swabs were daily collected and tested for the presence of N protein subgenomic RNA. At 3 and 7 dpi mice were also sacrificed and organs collected for molecular, histopathological and immune response profile investigations. The Δ680-689-B.1- infected mice exhibited reduced shedding, lower virulence at the lung level, and milder pulmonary lesions. In the lung, infection with Δ680-689-B.1 was associated with a significant lower expression of some cytokines at 3 dpi (IL-4, IL-27, and IL-28) and 7 dpi (IL-4, IL-27, IL-28, IFN-γ and IL-1α).

在这里，我们研究了一种独特的细胞适应 SARS-CoV-2 突变体的毒力特性，该突变体显示出包含刺突蛋白弗林蛋白酶切割位点的 10 个氨基酸缺失（Δ ₆₈₀ SPRAARSVAS ₆₈₉；Δ680-689-B.1）进行比较其亲本菌株（wt-B.1）和两个 Delta 变体（AY.122 和 AY.21）。IN 接种后，对转基因 K18-hACE2 小鼠进行为期 14 天的体重变化、致死率、临床评分监测，并每天收集口腔拭子并测试 N 蛋白亚基因组 RNA 的存在。在 3 dpi 和 7 dpi 时，还处死小鼠并收集器官用于分子、组织病理学和免疫反应谱研究。Δ680-689-B.1感染的小鼠表现出脱落减少、肺部毒力较低以及肺部病变较轻。在肺部，Δ680-689-B.1 感染与一些细胞因子在 3 dpi（IL-4、IL-27 和 IL-28）和 7 dpi（IL-4、IL-4）表达显着降低相关。 27、IL-28、IFN-γ 和 IL-1α）。