Abstract：
Cross-species transmission of coronaviruses has been continuously posing a major challenge to public health. Pigs, as the major animal reservoirs for many zoonotic viruses, frequently mediate viral transmission to humans. This study comprehensively mapped the relationship between human and porcine coronaviruses through in-depth bioinformatics analysis. We found that human coronavirus OC43 and porcine coronavirus PHEV share a close phylogenetic relationship, evidenced by high genomic homology, similar codon usage patterns and comparable tertiary structure in spike proteins. Inoculation of infectious OC43 viruses in organoids derived from porcine small and large intestine demonstrated that porcine intestinal organoids (pIOs) are highly susceptible to human coronavirus OC43 infection and support infectious virus production. Using transmission electron microscopy, we visualized OC43 viral particles in both intracellular and extracellular compartments, and observed abnormalities of multiple organelles in infected organoid cells. Robust OC43 infections in pIOs result in a significant reduction of organoids viability and widespread cell death. This study bears essential implications for better understanding the evolutionary origin of human coronavirus OC43, and provides a proof-of-concept for using pIOs as a model to investigate cross-species transmission of human coronavirus.
摘要：
冠状病毒的跨物种传播一直对公共卫生构成重大挑战。猪,作为许多人畜共患病毒的主要动物库，经常介导病毒传播给人类。本研究通过深入的生物信息学分析，全面绘制了人和猪冠状病毒之间的关系。我们发现人类冠状病毒OC43和猪冠状病毒PHEV具有密切的系统发育关系，高度的基因组同源性证明，相似的密码子使用模式和类似的三级结构的刺突蛋白。在源自猪小肠和大肠的类器官中接种感染性OC43病毒表明，猪肠类器官（pIOs）对人冠状病毒OC43感染高度敏感，并支持感染性病毒的产生。使用透射电子显微镜，我们在细胞内和细胞外区室观察到OC43病毒颗粒，并观察到感染的类器官细胞中多个细胞器的异常。pIOs中强健的OC43感染导致类器官活力的显著降低和广泛的细胞死亡。这项研究对于更好地理解人类冠状病毒OC43的进化起源具有重要意义，并为使用pIOs作为模型来研究人类冠状病毒的跨物种传播提供了概念证明。
