Duerr Ralf, Zhou Hao, Tada Takuya, Dimartino Dacia, Marier Christian, Zappile Paul, Wang Guiqing, Plitnick Jonathan, Griesemer Sara B, Girardin Roxanne, Machowski Jessica, Bialosuknia Sean, Lasek-Nesselquist Erica, Hong Samuel L, Baele Guy, Dittmann Meike, Ortigoza Mila B, Prasad Prithiv J, McDonough Kathleen, Landau Nathaniel R, St George Kirsten, Heguy Adriana
Department of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
iScience. 2023 Feb 17;26(2):106075. doi: 10.1016/j.isci.2023.106075. Epub 2023 Feb 13.
The emergence of recombinant viruses is a threat to public health, as recombination may integrate variant-specific features that together result in escape from treatment or immunity. The selective advantages of recombinant SARS-CoV-2 isolates over their parental lineages remain unknown. We identified a Delta-Omicron (AY.45-BA.1) recombinant in an immunosuppressed transplant recipient treated with monoclonal antibody Sotrovimab. The single recombination breakpoint is located in the spike N-terminal domain adjacent to the Sotrovimab binding site. While Delta and BA.1 are sensitive to Sotrovimab neutralization, the Delta-Omicron recombinant is highly resistant. To our knowledge, this is the first described instance of recombination between circulating SARS-CoV-2 variants as a functional mechanism of resistance to treatment and immune escape.
重组病毒的出现对公众健康构成威胁,因为重组可能整合特定变体特征,共同导致治疗逃逸或免疫逃逸。重组严重急性呼吸综合征冠状病毒2(SARS-CoV-2)分离株相对于其亲本谱系的选择优势仍然未知。我们在接受单克隆抗体索托维单抗治疗的免疫抑制移植受者中鉴定出一种德尔塔-奥密克戎(AY.45-BA.1)重组体。单一重组断点位于与索托维单抗结合位点相邻的刺突蛋白N端结构域。虽然德尔塔和BA.1对索托维单抗中和敏感,但德尔塔-奥密克戎重组体具有高度抗性。据我们所知,这是首次报道的循环SARS-CoV-2变体之间重组作为治疗抗性和免疫逃逸功能机制的实例。