Jane McKeating

Viruses are intracellular pathogens and understanding host pathways that define susceptibility to infection and disease are essential for the design of new therapies. Viral replication is shaped by the cellular microenvironment and current projects focus on the spatial mapping of infected cells at single-cell resolution to identify the key factors that regulate virus tissue tropism. RESEARCH THEMES Hepatitis viruses Chronic hepatitis B and D viruses are a major cause of liver disease and cancer, with limited curative treatments. The liver is a naturally hypoxic organ and we have identified a role for hypoxia inducible factors to activate viral transcription. Our goal is to understand the hepatocyte-intrinsic and extrinsic pathways that define host susceptibility to these viruses. The frequency of infected cells in the liver is low and bulk RNA-sequencing approaches frequently overlook their complex transcriptomes. We have developed spatial transcriptional profiling methods to identify HBV and HDV infected hepatocytes and their uninfected neighbours. When combined with single molecule resolution imaging of viral RNAs, these exciting technologies allow us to study virus-host interplay at unprecedented detail. Respiratory viruses Globally respiratory infections are responsible for approximately 4.25 million deaths/year (pre-COVID), mostly in children and the elderly. Viruses are responsible for the majority of these infections and developing broadly active tools to fight these viruses is a priority. We have shown that hypoxia suppresses SARS-CoV-2 replication and inflammatory responses. We have recently extended these observations to Respiratory Syncytial virus and shown our HIF mimetic drugs potently inhibit infection by activating innate sensing and Interferon-signalling.

[2025] Long-persisting SARS-CoV-2 spike-specific CD4+ T cells associated with mild disease and increased cytotoxicity post COVID-19, Liu G. et al, (2025), Nature Communications, 16 [2025] Episomal and integrated hepatitis B transcriptome mapping uncovers heterogeneity with the potential for drug-resistance, Harris JM. et al, (2025), Nature Communications, 16 [2025] Assessing the virological response to direct-acting antiviral therapies in the HBV cure programme., Lok J. et al, (2025), Virology, 605 [2024] Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics, Cross A. et al, (2024), eGastroenterology, 2, e100067 - e100067 [2024] Oxygen-dependent histone lysine demethylase 4 restricts hepatitis B virus replication, Harris JM. et al, (2024), Journal of Bio