Coxsackievirus B3 (CVB3) belongs to the enteroviruses, which are a well-known cause of acute and chronic myocarditis, primarily infecting cardiac myocytes. As primary human cardiomyocytes are difficult to obtain, viral myocarditis is quite frequently studied in vitro in different non-cardiac and cardiac-like cell lines. Recently, cardiomyocytes that have been differentiated from human-induced pluripotent stem cells have been described as a new model system to study CVB3 infection. Here, we compared iCell^® Cardiomyocytes with other cell lines that are commonly used to study CVB3 infection regarding their susceptibility and patterns of infection and the mode of cell death. iCell^® Cardiomyocytes, HeLa cells, HL-1 cells and H9c2 cells were infected with CVB3 (Nancy strain). The viral load, CVB3 RNA genome localization, VP1 expression (including the intracellular localization), cellular morphology and the expression of cell death markers were compared. The various cell lines clearly differed in their permissiveness to CVB3 infection, patterns of infection, viral load, and mode of cell death. When studying the mode of cell death of CVB3-infected iCell^® Cardiomyocytes in more detail, especially regarding the necroptosis key players RIPK1 and RIPK3, we found that RIPK1 is cleaved during CVB3 infection. iCell^® Cardiomyocytes represent well the natural host of CVB3 in the heart and are thus the most appropriate model system to study molecular mechanisms of CVB3-induced myocarditis in vitro. Doubts are raised about the suitability of commonly used cell lines such as HeLa cells, HL-1 cells and H9c2 cells to evaluate molecular pathways and processes occurring in vivo in enteroviral myocarditis.

中文翻译：

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柯萨奇病毒 B3 诱导心肌炎的体外模型系统：常用细胞系的比较和 CVB3 感染的 iCell® 心肌细胞的表征

柯萨奇病毒 B3 (CVB3) 属于肠道病毒，是众所周知的急性和慢性心肌炎病因，主要感染心肌细胞。由于原代人心肌细胞难以获得，病毒性心肌炎经常在体外不同的非心脏和心脏样细胞系中进行研究。最近，已从人诱导的多能干细胞分化的心肌细胞被描述为研究 CVB3 感染的新模型系统。在这里，我们将 iCell ^®心肌细胞与其他常用于研究 CVB3 感染的细胞系进行比较，了解它们的易感性和感染模式以及细胞死亡模式。iCell® ^_用CVB3（Nancy株）感染心肌细胞、HeLa细胞、HL-1细胞和H9c2细胞。比较病毒载量、CVB3 RNA基因组定位、VP1表达（包括细胞内定位）、细胞形态和细胞死亡标志物的表达。各种细胞系在对 CVB3 感染的许可、感染模式、病毒载量和细胞死亡方式方面明显不同。在更详细地研究 CVB3 感染的 iCell ^®心肌细胞的细胞死亡模式时，特别是关于坏死性凋亡关键参与者 RIPK1 和 RIPK3，我们发现 RIPK1 在 CVB3 感染期间被切割。iCell® ^_心肌细胞很好地代表了心脏中 CVB3 的天然宿主，因此是研究 CVB3 诱导的体外心肌炎分子机制的最合适的模型系统。人们对常用的细胞系（如 HeLa 细胞、HL-1 细胞和 H9c2 细胞）是否适合评估肠病毒性心肌炎体内发生的分子途径和过程提出了质疑。