Moriyama Miyu, Lucas Carolina, Monteiro Valter Silva, Iwasaki Akiko
bioRxiv. 2022 Dec 23:2022.05.04.490614. doi: 10.1101/2022.05.04.490614.
SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress MHC I expression. We identified several viral genes that contribute to the suppression of MHC I expression. Notably, MHC-I upregulation was strongly inhibited after SARS-CoV-2 infection in vivo. While earlier VOCs possess similar capacity as the ancestral strain to suppress MHC I, Omicron subvariants exhibit a greater ability to suppress surface MHC-I expressions. Collectively, our data suggest that, in addition to escape from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的关注变异株（VOCs）具有一些突变，这些突变赋予了刺突蛋白对中和抗体的抗性，并与突破性感染和再次感染有关。相比之下，关于VOCs逃避CD8+T细胞介导的免疫的情况，人们了解较少。在此，我们证明所有SARS-CoV-2 VOCs都具有抑制MHC I表达的能力。我们鉴定出了几个有助于抑制MHC I表达的病毒基因。值得注意的是，在体内SARS-CoV-2感染后，MHC-I的上调受到强烈抑制。虽然早期的VOCs与原始毒株具有相似的抑制MHC I的能力，但奥密克戎亚变体表现出更强的抑制表面MHC-I表达的能力。总体而言，我们的数据表明，除了逃避中和抗体外，奥密克戎亚变体导致突破性感染和再次感染的成功可能部分归因于其对T细胞识别的优化逃避。
