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

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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 A recent publication as well as unpublished preliminary data show that low oxygen conditions dampen cellular immune responses through degradation of host factors involved and specific metabolites.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.