Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Microbiology, Harvard Medical School, Boston, MA 02215, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Microbiology, Harvard Medical School, Boston, MA 02215, USA.
Cell Rep. 2022 Jun 14;39(11):110924. doi: 10.1016/j.celrep.2022.110924. Epub 2022 May 20.
The recently emerged B.1.1.529 (Omicron) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant has a highly divergent spike (S) glycoprotein. We compared the functional properties of B.1.1.529 BA.1 S with those of previous globally prevalent SARS-CoV-2 variants, D614G and B.1.617.2. Relative to these variants, B.1.1.529 S exhibits decreases in processing, syncytium formation, virion incorporation, and ability to mediate infection of cells with high TMPRSS2 expression. B.1.1.529 and B.1.617.2 S glycoproteins bind ACE2 with higher affinity than D614G S. The unliganded B.1.1.529 S trimer is less stable at low temperatures than the other SARS-CoV-2 Ss, a property related to its more "open" S conformation. Upon ACE2 binding, the B.1.1.529 S trimer sheds S1 at 37°C, but not at 0°C. B.1.1.529 pseudoviruses are relatively resistant to neutralization by sera from patients with coronavirus disease 2019 (COVID-19) and vaccinees. These properties of the B.1.1.529 S glycoprotein likely influence the transmission, cytopathic effects, and immune evasion of this emerging variant.
最近出现的 B.1.1.529（奥密克戎）严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变体具有高度分化的刺突（S）糖蛋白。我们比较了 B.1.1.529 BA.1 S 与之前全球流行的 SARS-CoV-2 变体 D614G 和 B.1.617.2 的功能特性。与这些变体相比，B.1.1.529 S 的加工、合胞体形成、病毒粒子掺入以及介导高 TMPRSS2 表达细胞感染的能力降低。B.1.1.529 和 B.1.617.2 S 糖蛋白与 ACE2 的结合亲和力高于 D614G S。未结合的 B.1.1.529 S 三聚体在低温下比其他 SARS-CoV-2 S 更不稳定，这种特性与其更“开放”的 S 构象有关。在 ACE2 结合后，B.1.1.529 S 三聚体在 37°C 下但不在 0°C 下脱落 S1。B.1.1.529 假病毒对来自 2019 年冠状病毒病（COVID-19）患者和疫苗接种者的血清的中和作用具有相对抗性。B.1.1.529 S 糖蛋白的这些特性可能影响这种新兴变体的传播、细胞病变效应和免疫逃逸。
