Long-Term Expansion of Porcine Intestinal Organoids Serves as an in vitro Model for Swine Enteric Coronavirus Infection

文献类型： 外文期刊

第一作者： Zhang, Min

作者： Zhang, Min;Tong, Guangzhi;Zhang, Min;Lv, Lilei;Cai, Hongming;Gao, Fei;Yu, Lingxue;Jiang, Yifeng;Tong, Wu;Li, Liwei;Li, Guoxin;Tong, Guangzhi;Liu, Changlong;Cai, Hongming;Li, Yanhua;Gao, Fei;Yu, Lingxue;Jiang, Yifeng;Tong, Wu;Li, Liwei;Li, Guoxin;Tong, Guangzhi;Liu, Changlong

作者机构：

关键词： long-term 3D culture; porcine intestinal organoids; swine enteric coronaviruses; interferon-stimulated genes; immune suppression

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：6.064； 五年影响因子：6.843 ）

ISSN：

年卷期： 2022 年 13 卷

页码：

收录情况： SCI

摘要： A reliable and reproducible model in vitro for swine enteric coronaviruses infection would be intestinal models that support virus replication and can be long-term cultured and manipulated experimentally. Here, we designed a robust long-term culture system for porcine intestinal organoids from the intestinal crypt or single LGR5(+) stem cell by combining previously defined insights into the growth requirements of the intestinal epithelium of humans. We showed that long-term cultured swine intestinal organoids were expanded in vitro for more than 6 months and maintained the potential to differentiate into different types of cells. These organoids were successfully infected with porcine enteric coronavirus, including porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), and were capable of supporting virus replication and progeny release. RNA-seq analysis showed robust induction of transcripts associated with antiviral signaling in response to enteric coronavirus infection, including hundreds of interferon-stimulated genes and cytokines. Moreover, gene set enrichment analysis indicated that PEDV infection could suppress the immune response in organoids. This 3D intestinal organoid model offers a long-term, renewable resource for investigating porcine intestinal infections with various pathogens.

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