SARS-CoV-2奥密克戎BA.2.86和JN.1在人近端肠上皮中扩大嗜性
SARS-CoV-2 Omicron BA.2.86 and JN.1 expand tropism in human proximal intestinal epithelium.
摘要(中文译文)
奥密克戎SARS-CoV-2已分化为多个亚谱系，由于背景人群免疫的影响，对其内在表型的评估变得复杂。我们利用人支气管和肺外植体、气道类器官、结肠细胞和近端肠道肠类器官，比较了从BA.1到JN.1各变异株的复制能力和生物学特征。XBB.1.5和EG.5.1在呼吸组织中的复制滴度高于BA.2.86和JN.1，表明其呼吸道适应性增强。EG.5.1表现出双重细胞进入途径，并在肺泡上皮细胞中复制更强，支持其肺嗜性和致病性增加。相比之下，BA.2.86和JN.1在气道中依赖TMPRSS2介导的进入途径。值得注意的是，BA.2.86和JN.1在近端肠道肠类器官中的复制效率高于EG.5.1，且依赖ACE2和TMPRSS2，但在结肠细胞中并非如此。JN.1表现出增强的肠道嗜性，同时促炎细胞因子诱导有限，提示其具有粪口传播潜力。本研究表明，XBB.1.5和EG.5.1具有更强的传播性和致病潜力，而BA.2.86和JN.1则表现出增强的肠道适应性。
Abstract
Omicron SARS-CoV-2 has diversified into multiple sub-lineages, complicating assessment of their intrinsic phenotypes due to background population immunity. We compare replication and biological characteristics of variants from BA.1 to JN.1 using human bronchial and lung explants, airway organoids, colon cells, and proximal intestinal enteroids. XBB.1.5 and EG.5.1 achieve higher replication titres in respiratory tissues than BA.2.86 and JN.1, indicating enhanced respiratory fitness. EG.5.1 displays dual cell-entry pathways and greater replication in alveolar epithelial cells, supporting increased lung tropism and pathogenicity. In contrast, BA.2.86 and JN.1 rely on TMPRSS2-mediated entry in airways. Notably, BA.2.86 and JN.1 replicate more efficiently than EG.5.1 in proximal intestinal enteroids in an ACE2- and TMPRSS2-dependent manner, but not in colon cells. JN.1 exhibits elevated intestinal tropism with limited proinflammatory cytokine induction, suggesting potential for faecal transmission. Here we show XBB.1.5 and EG.5.1 greater transmissibility and severity potential whereas BA.2.86 and JN.1 exhibit enhanced intestinal adaptation.
如何引用
AMA
Kenrie Py Hui, John Cw Ho, Ka-Chun Ng, Jenny Cm Chan, Taylor Wc Ho, Rachel Hh Ching, et al. SARS-CoV-2 Omicron BA.2.86 and JN.1 expand tropism in human proximal intestinal epithelium.. Nature communications. 2026; doi:10.1038/s41467-026-74111-y.
APA
Kenrie Py Hui, John Cw Ho, Ka-Chun Ng, Jenny Cm Chan, Taylor Wc Ho, Rachel Hh Ching, et al (2026). SARS-CoV-2 Omicron BA.2.86 and JN.1 expand tropism in human proximal intestinal epithelium.. Nature communications. https://doi.org/10.1038/s41467-026-74111-y
GB/T 7714
Kenrie Py Hui, John Cw Ho, Ka-Chun Ng, Jenny Cm Chan, Taylor Wc Ho, Rachel Hh Ching, et al. SARS-CoV-2 Omicron BA.2.86 and JN.1 expand tropism in human proximal intestinal epithelium.[J]. Nature communications, 2026 doi:10.1038/s41467-026-74111-y.
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