The Intersection between Cell-Intrinsic Innate Immunity and Metabolic Sensing

我所在部门的所有工作都是从2017年2月开始的，所以目前还没有基于CCR的成果报告。尽管如此，该项目的目标和宗旨已经明确。我们在转化的上皮细胞系上使用雷帕霉素的初步工作揭示了mTOR抑制赋予4至20倍的感染增强，这取决于病毒攻击的性质，特别是病毒进入细胞的途径。此外，我们发现，雷帕霉素依赖性增强感染逆转内体酸化抑制剂（v-ATP酶），揭示了增强需要通过溶酶体途径的细胞因子的主动降解。我们目前正在确定对细胞易感性的影响是否与巨自噬直接相关，巨自噬是一种由mTOR控制的分解代谢过程。此外，我们计划抑制mTOR上游和下游的PI 3 K-Akt-mTOR通路，以缩小在这些环境中直接参与控制病毒感染的细胞蛋白。

All work in my section began in February 2017, so there are no CCR-based accomplishments to report yet. Nonetheless, the goals and objectives of the project have crystallized. Our preliminary work using rapamycin on transformed epithelial cell lines has revealed that mTOR inhibition confers a 4- to 20-fold enhancement of infection, depending on the nature of the virus challenge and, specifically, the route of virus entry into cells. Furthermore, we found that the rapamycin-dependent enhancement of infection is reversed by inhibitors of endosomal acidification (v-ATPase), revealing that the enhancement requires active degradation of cellular factors via the lysosomal pathway. We are currently determining whether the effect on cellular susceptibility is directly linked to macroautophagy, a catabolic process controlled by mTOR. Moreover, we plan to inhibit the PI3K-Akt-mTOR pathway upstream and downstream of mTOR to narrow down the cellular proteins directly implicated in the control of virus infection in these settings.