Infection of bat and human intestinal organoids by SARS-CoV-2
Infection of bat and human intestinal organoids by SARS-CoV-2
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DOI：
10.1038/s41591-020-0912-6
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发表时间：
2020-05-13
期刊：
影响因子：
82.9
通讯作者：
Yuen, Kwok Yung
中科院分区：
文献类型：
--
作者：
Zhou Jie;Li Cun;Yuen, Kwok Yung
2019年1,2月，一种新型冠状病毒--严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在中国武汉出现，并在全球传播（1，2）。截至2020年4月16日，2019冠状病毒病（COVID-19）确诊病例数已超过200万例。基于全基因组序列分析，SARS-CoV-2与在马蹄蝙蝠中鉴定的SARS相关冠状病毒具有高度同源性（1，2）。在这里，我们展示了来自中华菊头蝠种的马蹄蝙蝠的可膨胀肠类器官的建立和表征，其可以重演蝙蝠肠上皮。这些蝙蝠肠状体对SARS-CoV-2感染完全敏感，并维持强大的病毒复制。一些COVID-19患者出现胃肠道症状以及在粪便标本中检测到病毒RNA表明，SARS-CoV-2可能导致肠道感染（除呼吸道感染外）（3，4）。在这里，我们证明了SARS-CoV-2在人类肠道类器官中的活跃复制，并从一名结肠炎COVID-19患者的粪便标本中分离出感染性病毒。总之，我们建立了第一个可扩展的蝙蝠肠上皮细胞类器官培养系统，并提出了SARS-CoV-2可以感染蝙蝠肠细胞的证据。SARS-CoV-2在人类肠道类器官中的复制表明，人类肠道可能是SARS-CoV-2的传播途径之一。蝙蝠和人类肠道类器官可以支持SARS-CoV-2的复制，这为进一步研究SARS-CoV-2的生命周期和探索COVID-19肠道感染的潜在机制奠定了基础。
A novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally(1,2). As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats(1,2). Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection(3,4). Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.