Intestinal organoids as an infection model Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an influenza-like disease with a respiratory transmission route; however, patients often present with gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Moreover, the virus has been detected in anal swabs, and cells in the inner-gut lining express the receptor that SARS-CoV-2 uses to gain entry to cells. Lamers et al. used human intestinal organoids, a “mini-gut” cultured in a dish, to demonstrate that SARS-CoV-2 readily replicates in an abundant cell type in the gut lining—the enterocyte—resulting in the production of large amounts of infective virus particles in the intestine. This work demonstrates that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut. Science, this issue p. 50 SARS-CoV-2 infects enterocytes in human small intestinal organoids. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2, as demonstrated by confocal and electron microscopy. Enterocytes produced infectious viral particles, whereas messenger RNA expression analysis of hSIOs revealed induction of a generic viral response program. Therefore, the intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology.

中文翻译：

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SARS-CoV-2 可有效感染人类肠道肠细胞


肠道类器官作为感染模型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起一种通过呼吸道传播途径的流感样疾病；然而，患者常出现腹泻、呕吐、腹痛等胃肠道症状。此外，在肛门拭子中检测到了该病毒，肠内壁细胞表达 SARS-CoV-2 用来进入细胞的受体。拉默斯等人。使用人类肠道类器官（一种在培养皿中培养的“迷你肠道”）来证明 SARS-CoV-2 很容易在肠道内壁丰富的细胞类型（肠上皮细胞）中复制，从而产生大量感染性病毒颗粒在肠道中。这项工作表明，肠道类器官可以作为了解 SARS-CoV-2 生物学和肠道感染性的模型。科学，本期第 14 页。 50 SARS-CoV-2 感染人类小肠类器官中的肠细胞。严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 可引起 2019 冠状病毒病 (COVID-19)，这是一种类似流感的疾病，主要通过呼吸道传播感染肺部。然而，临床证据表明肠道可能是另一个病毒靶器官。事实上，SARS-CoV-2 受体血管紧张素转换酶 2 (ACE2) 在分化的肠上皮细胞上高度表达。共聚焦和电子显微镜证明，在人类小肠类器官 (hSIO) 中，肠细胞很容易被 SARS-CoV 和 SARS-CoV-2 感染。肠细胞产生感染性病毒颗粒，而 hSIO 的信使 RNA 表达分析揭示了通用病毒反应程序的诱导。 因此，肠上皮支持 SARS-CoV-2 复制，而 hSIO 可以作为冠状病毒感染和生物学的实验模型。