Hübner Denise, Jahn Kristin, Pinkert Sandra, Böhnke Janik, Jung Matthias, Fechner Henry, Rujescu Dan, Liebert Uwe Gerd, Claus Claudia
Institute of Virology, University of Leipzig , Johannisallee 30, 04103 Leipzig, Germany.
Institute of Virology and Faculty of Life Sciences, University of Leipzig , Talstrasse 33, 04103 Leipzig, Germany.
ACS Infect Dis. 2017 Dec 8;3(12):886-897. doi: 10.1021/acsinfecdis.7b00103. Epub 2017 Oct 26.
Human induced pluripotent stem cell (iPSC) lines are a promising model for the early phase of human embryonic development. Here, their contribution to the still incompletely understood pathogenesis of congenital virus infections was evaluated. The infection of iPSC lines with miscarriage-associated coxsackievirus B3 (CVB3) and measles virus (MV) was compared to the efficient teratogen rubella virus (RV). While CVB3 and MV were found to be cytopathogenic on iPSC lines, RV replicated without impairment of iPSC colony morphology and integrity. This so far outstanding course of infection enabled maintenance of RV-infected iPSC cultures over several passages and their subsequent differentiation to ectoderm, endoderm, and mesoderm. A modification of the metabolic profile of infected iPSC lines was the only common aspect for all three viruses. This study points toward two important aspects. First, iPSC lines represent a suitable cell culture model for early embryonic virus infection. Second, metabolic activity represents an important means for evaluation of pathogen-associated alterations in iPSC lines.
人诱导多能干细胞(iPSC)系是人类胚胎发育早期阶段的一种有前景的模型。在此,评估了它们对先天性病毒感染发病机制(仍未完全了解)的影响。将与流产相关的柯萨奇病毒B3(CVB3)和麻疹病毒(MV)感染iPSC系的情况与高效致畸剂风疹病毒(RV)进行了比较。虽然发现CVB3和MV对iPSC系具有细胞致病性,但RV在不损害iPSC集落形态和完整性的情况下进行复制。迄今为止这种显著的感染过程使得感染RV的iPSC培养物能够传代培养数代,并随后分化为外胚层、内胚层和中胚层。感染的iPSC系代谢谱的改变是所有三种病毒唯一的共同特征。本研究指向两个重要方面。第一,iPSC系代表了早期胚胎病毒感染的合适细胞培养模型。第二,代谢活性是评估iPSC系中病原体相关改变的重要手段。