Stemness and the cellular response to virus infection

项目总结 考虑到几乎无限的利基市场和扩张的时间，每一种可能的进化情景都参与了进来 塑造了我们今天所看到的，也许是独立的，多次，在许多地方。可以说，世界上最 这种进化生命过程的强大推动力是病毒和宿主之间的斗争，这导致了非常 多样化的防御策略。有趣的是，尽管细胞对病毒感染的反应被认为是 在任何一个给定的物种中都是如此，越来越多的证据表明哺乳动物干细胞具有独特的策略来 对抗有别于身体所有其他细胞的病毒。这种观察在很大程度上是基于这一发现 这些细胞可以成功地阻止生产性病毒感染，尽管缺乏产生或 对I型干扰素有反应。在这个探索性的R21中，我们试图确定这一活动的分子基础。 为此，我们专注于使用原代成纤维细胞和重新编程的诱导多能性的体外模型 AIM 1中的干细胞(IPS)以及一个体内模型来鉴定和表征 AIM 2的生产性病毒感染。

PROJECT SUMMARY Given the virtually infinite niches and time to expand, every evolutionary scenario possible has had a hand in shaping what we see today, perhaps independently many times and in many places. Arguably, one of the most powerful drivers of this evolutionary life process is the struggle between virus and host that has resulted in very diverse defensive strategies. Interestingly, while the cellular response to virus infection was thought to be uniform in any one given species, evidence is mounting that mammalian stem cells have a unique strategy to combat virus that is distinct from all other cells of the body. This observation is largely based on the finding that these cells can successfully block productive virus infection, despite lacking the capacity to produce or respond to Type I interferon. In this exploratory R21, we seek to ascertain the molecular basis for this activity. To this end, we focus on an ex vivo model using primary fibroblasts and reprogrammed induced pluripotent stem (iPS) cells in Aim 1 as well as an in vivo model to identify and characterize resident stem cells during a productive virus infection in Aim 2.