Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants.

Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants.
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DOI:
10.1038/s41467-023-38867-x
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发表时间:
2023-06-03
影响因子:
16.6
通讯作者:
van Bakel, Harm
van Bakel, Harm
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gonzalez-Reiche, Ana;Alshammary, Hala;Schaefer, Sarah;Patel, Gopi F.;Polanco, Jose C.;Carreno, Juan Manuel;Amoako, Angela;Rooker, Aria;Cognigni, Christian;Floda, Daniel;van de Guchte, Adriana;Khalil, Zain;Farrugia, Keith;Assad, Nima;Zhang, Jian;Alburquerque, Bremy A.;Sominsky, Levy;Gleason, Charles;Srivastava, Komal;Sebra, Robert;Ramirez, Juan David;Banu, Radhika;Shrestha, Paras;Krammer, Florian;Paniz-Mondolfi, Alberto;Sordillo, Emilia Mia;Simon, Viviana;van Bakel, Harm

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据报道,在免疫功能低下的个体和接受免疫调节治疗的人群中,持续性严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染。虽然宿主内进化已被记录,但缺乏随后传播和持续逐步适应的直接证据。在这里,我们描述了连续的持续性SARS-CoV-2感染的三个人,导致出现,前向传播,并继续演变的一个新的Omicron亚系,BA.1.23,在8个月的时间。最初传播的BA.1.23变异体编码刺突蛋白内的7个额外氨基酸取代(E96 D、R346 T、L455 W、K458 M、A484 V、H681 R、A688 V),并显示出对来自加强和/或Omicron BA.1感染的研究参与者的血清的中和的实质性抗性。随后继续的BA.1.23复制导致刺突蛋白(S254 F、N448 S、F456 L、M458 K、F981 L、S982 L)以及五种其他病毒蛋白中的额外取代。我们的研究结果不仅表明Omicron BA.1谱系可以进一步偏离其已经异常突变的基因组,而且持续感染的患者可以传播这些病毒变体。因此,迫切需要实施预防SARS-CoV-2长期复制的策略,并限制新出现的耐中和变体在脆弱患者中的传播。对SARS-CoV-2宿主内进化以及持续感染背景下的后续传播和适应的理解有限。在这里,作者描述了连续的持续性SARS-CoV-2感染,导致了一种新的Omicron BA.1.23谱系的出现、传播和进一步进化。
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients. There is limited understanding of SARS-CoV-2 intra-host evolution and subsequent transmission and adaptations in the context of persistent infection. Here, the authors describe sequential persistent SARS-CoV-2 infections that led to the emergence, transmission and further evolution of a novel Omicron BA.1.23 lineage.
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影响因子: 16.6
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影响因子: 56.9
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影响因子: 10.7
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