Abstract:
The emergence of new SARS-CoV-2 variants and the replacement of preceding isolates have been observed through B.1.1.7, B.1.351, B.1.617.2, and B.1.1.529 lineages (corresponding to alpha, beta, delta, and omicron variants of concern (VoC), respectively). However, there is still a lack of biological evidence to which extent those VoC differ from the ancestral lineages. By exploiting human airway epithelial cell (HAEC) cultures, which closely resemble the human airway architecture and physiology, we report distinctive SARS-CoV-2 tropism in different respiratory tissues. In general, SARS-CoV-2 VoC predominantly infect and replicate in HAEC better than the progenitor USA-WA1 isolate or the BavPat1 isolate, which contains the D614G mutation, even though there is little to no difference between variants regarding their infectivity (i.e., virion-per-vRNA copy ratio). We also observe differential tissue-specific innate immunity activation between the upper and lower respiratory tissues in the presence of the virus. Our study provides better comprehension of the behavior of the different VoC in this physiologically relevant ex vivo model.
摘要:
通过B.1.1.7、B.1.351、B.1.617.2和B.1.1.29谱系(对应于α,beta,delta,和关注的omicron变体(VoC),分别)。然而,仍然缺乏生物学证据,这些VoC在多大程度上与祖先血统不同。通过利用人气道上皮细胞(HAEC)培养,非常类似于人类的气道结构和生理学,我们报告了不同呼吸组织中独特的SARS-CoV-2嗜性。总的来说,SARS-CoV-2VoC在HAEC中的主要感染和复制优于祖先USA-WA1分离株或BavPat1分离株,其中包含D614G突变,即使变体之间在其传染性方面几乎没有差异(即,病毒体每vRNA拷贝比)。我们还观察到在存在病毒的情况下,上呼吸道和下呼吸道组织之间的组织特异性先天免疫激活差异。我们的研究提供了对这种生理相关离体模型中不同VoC行为的更好理解。