Understanding the effect of low oxygen conditions on innate immune responses to Zika virus infection

病毒感染的成功受到细胞微环境的影响，其中一个重要因素是氧气供应。大多数体外系统不能模拟人体组织中的生理氧气条件。体外系统通常在常压(20%)氧气中进行，而大多数器官的氧气浓度在1%到5%之间变化。最近发表的以及未发表的初步数据表明，低氧条件通过降解所涉及的宿主因子和特定代谢物来抑制细胞免疫反应。为什么某些病毒家族优先感染特定的组织，这可能反映了它们对这些特定条件的适应。在这个项目中，我将模拟更生理的氧气条件，并研究寨卡病毒(ZIKV)复制和宿主先天免疫反应在这些条件下是如何改变的。ZIKV感染与新生儿的神经系统疾病有关，鉴于目前缺乏治疗，迫切需要了解调节ZIKV复制的宿主途径。这个项目将研究生理低氧条件下的代谢和免疫信号之间的相互作用，以及这是如何调节ZIKV的繁殖和传播的。该项目可能为发现治疗这种人类病原体和该病毒家族其他成员的新治疗靶点铺平道路。

The success of a virus infection is affected by the cellular microenvironment and one important factor is the oxygen supply. The majority of in vitro systems do not model physiological oxygen conditions in human tissue. In vitro systems are usually performed at atmospheric (20%) oxygen, whereas the oxygen concentration in most organs varies between 1% and 5%. A recent publication as well as unpublished preliminary data show that low oxygen conditions dampen cellular immune responses through degradation of host factors involved and specific metabolites. Why certain virus families preferentially infect a specific tissue might reflect their adaptation to these specific conditions. In this project I will model oxygen conditions that resemble a more physiological scenario and investigate how Zika virus (ZIKV) replication and host innate immune responses are changed under these conditions. ZIKV infections are associated with neurological disorders in newborn infants and given the current lack of treatments, there is an urgent need to understand host pathways that regulate ZIKV replication. This project will study the interplay between metabolism in physiological hypoxic conditions and immune signalling, and how this regulates ZIKV reproduction and spread. This project may pave the way to discovering new therapeutic targets for treating this human pathogen and other members of this family of viruses.