Defining the role of hypoxia inducible factors in viral replication and pathogenesis (360G-Wellcome-200838_Z_16_Z)
Viruses are obligate parasites that have evolved to manipulate their host to their advantage. Hypoxia inducible factors (HIFs) are regulated by oxygen-dependent and independent stress signals and control genes involved in energy metabolism, inflammation and angiogenesis. HIF-signalling pathways are perturbed in many diseases including cancer and inflammatory conditions, however, their role in viral infection is poorly understood. My group’s recent discovery that HIF-1alpha regulates HBV and HCV infection highlights an unexpected role for these transcription factors in the replicative lifecycle of these liver-tropic DNA and RNA oncogenic viruses. We have shown that HBV and HCV activate HIF and associated-transcriptional activity, suggesting a role in viral-associated cancer. We will use state-of-art HBV and HCV replication model systems, inducible-HIF hepatocellular knock-out mice, HBV transgenic mice and samples from human HCC to dissect the role of HIFs in virus replication and pathogenesis. Of note, several other oncogenic viruses (EBV, KSHV, HPV) also stabilize HIF, highlighting a convergence of diverse viruses targeting this pathway. Since viruses replicate in tissues with variable oxygen tensions in vivo, understanding the role HIFs play in viral replication will inform the design of physiologically relevant systems to model virus-host interactions.
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Grant Details
Amount Awarded | 1507759 |
Applicant Surname | McKeating |
Approval Committee | Science Interview Panel |
Award Date | 2016-04-05T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 200838/Z/16/Z |
Lead Applicant | Prof Jane McKeating |
Partnership Value | 1507759 |
Planned Dates: End Date | 2023-09-01T00:00:00+00:00 |
Planned Dates: Start Date | 2017-08-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |