Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater.

Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater.
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DOI:
10.1038/s41467-022-28246-3
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发表时间:
2022-02-03
影响因子:
16.6
通讯作者:
Dennehy JJ
Dennehy JJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Smyth DS;Trujillo M;Gregory DA;Cheung K;Gao A;Graham M;Guan Y;Guldenpfennig C;Hoxie I;Kannoly S;Kubota N;Lyddon TD;Markman M;Rushford C;San KM;Sompanya G;Spagnolo F;Suarez R;Teixeiro E;Daniels M;Johnson MC;Dennehy JJ

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跟踪SARS-CoV-2的遗传多样性是非常有必要的,因为多样化选择可能导致出现对自然获得的或疫苗诱导的免疫力具有抗性的新变体。为了监测纽约市(NYC)新变异体的存在,我们对从纽约市废水中分离的SARS-CoV-2的S蛋白的大部分受体结合结构域编码序列进行了深度测序。在这里,我们报告检测到越来越多的新的隐藏的SARS-CoV-2谱系在GISAID的EpiCoV数据库中没有识别。这些谱系包含在临床样本中很少观察到的突变,包括Q493 K、Q498 Y、E484 A和T572 N,并且与关注的Omicron变体共享许多突变。其中一些突变通过允许表达人、小鼠或大鼠ACE 2受体的细胞感染来扩大SARS-CoV-2假病毒的嗜性。最后,含有这些谱系的刺突氨基酸序列的假病毒对不同类别的受体结合结构域中和单克隆抗体具有抗性。我们为这些谱系的异常存在提供了几种假设,包括这些谱系来源于未采样的人类COVID-19感染或它们表明存在非人类动物宿主的可能性。为了监测纽约市新的SARS-CoV-2变异体的存在,Smyth等人对废水样品中S蛋白的受体结合结构域进行了深度测序,发现了含有影响ACE 2向性的突变并显示抗体中和作用降低的新的隐蔽谱系。
Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID’s EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations with the Omicron variant of concern. Some of these mutations expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor. Finally, pseudoviruses containing the spike amino acid sequence of these lineages were resistant to different classes of receptor binding domain neutralizing monoclonal antibodies. We offer several hypotheses for the anomalous presence of these lineages, including the possibility that these lineages are derived from unsampled human COVID-19 infections or that they indicate the presence of a non-human animal reservoir. To monitor the presence of novel SARS-CoV-2 variants in New York City, Smyth et al. perform deep-sequencing of the receptor binding domain of S protein in wastewater samples and find novel cryptic lineages containing mutations affecting ACE2-tropism and showing decreased neutralization by antibodies.
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