Madeline Carey
DPhil Student
My research is focused on manipulating the cellular oxygen sensing pathway as a novel approach to regulate BK polyomavirus replication in the transplanted kidney. BK polyomavirus (BKV), a prevalent renal-tropic DNA virus, can cause severe complications in kidney transplant patients, such as nephropathy and graft rejection. Treatment options are limited, and the cellular determinants of BKV reactivation in transplant patients remain undefined. The microenvironment of the renal tubule experiences considerably reduced oxygen levels compared with other organs. In this context, the hypoxia-inducible-factor (HIF) signalling pathway orchestrates a transcriptional response to enable cellular adaptation to hypoxia. A notable consequence is suppression of the innate antiviral immune response.
Preliminary data show that culturing BKV-infected cells in oxygen tensions mimicking renal physiology significantly potentiates viral replication, correlating with the concurrent downregulation of the innate immune response. We hypothesise that HIF-induced suppression of innate sensing creates a cellular microenvironment more permissive to BKV replication. Through employing a multi-disciplinary approach integrating molecular virology, hypoxia biology, and spatial transcriptomics, this research aims to evaluate: (a) the interaction between BKV replication and the cellular hypoxic response and (b) potential therapeutic manipulation of this pathway as an antiviral approach.