Chronic Hepatitis B

• New hepatitis B study reveals how viruses adapt to low-oxygen environments, such as those found deep within the liver, opening up possible new therapeutic targets for liver pathogens.
• Oxford researchers identify hypoxia inducible factors (HIFs) as playing an important role in regulation of editing of viral RNAs in low oxygen conditions.

The University of Oxford’s research of hypoxic modulation of m6A-RNA (effect of hypoxia on cellular RNA modification levels) allows for changes in the m6A modification to regulate stem cell pluripotency during embryonic development that might prove to be a solution

Chronic hepatitis B (CHB) is one of the world’s most economically important diseases, with 2 billion people exposed to the virus during their lifetime resulting in a global burden of >290 million infections

Hepatitis B virus (HBV) replicates in the liver and chronic infection can result in progressive liver disease, cirrhosis and liver cancer. At present there are no curative treatments due to the persistence of HBV DNA and a dysfunctional viral-specific immune response. Understanding the pathways that influence viral gene expression will illuminate new therapeutic approaches.

Oxygen is essential to all living things and its availability varies in different tissues. The liver experiences a gradient of oxygen from 3-8% between the pericentral and periportal regions. Cells adapt to low oxygen through an orchestrated transcriptional response regulated by hypoxia inducible factors (HIFs). When oxygen is abundant, HIFα subunits are targeted for proteasomal degradation, however, under low oxygen conditions HIFs regulate a plethora of cellular processes. This new study investigates the role of methyl-N6-adenosine (m6A) modifications of HBV RNAs under hepatic oxygen levels and uncovers a new role for HIFs to regulate m6A-modified viral RNAs, impacting their stability and abundance in infected cells. These observations highlight a role for HIFs to regulate the editing of viral RNAs that may provide new therapeutic targets and be widely applicable to other liver tropic pathogens.

Prof McKeating chair of Molecular Virology in the Nuffield Department of Medicine, University of Oxford said: It’s fascinating to see how viruses adapt to their environment and reveal their ‘achilles’ heel’ for the potential discovery of new antiviral agents. The University of Oxford’s research on the hypoxic modulation of m6A-RNA (effect of hypoxia on cellular RNA modification levels) may provide a mechanism for altered gene expression in liver cancer.

Supporting these numerous other studies showed that hypoxic modulation of m6A-RNA is dependent on both the tissue and cell type.

Further information:
Contact details
Thank you for your interest in the trial, we hope this information sheet has answered all of your questions. If you would like further information about taking part in research please visit the following website: [http://www.nhs.uk/conditions/clinical-trials/pages/introduction.aspx].

For independent advice about taking part in this study, you may wish to contact your GP. If you would like to speak to one of our study doctors or Professor Helen McShane (Chief Investigator) to discuss any aspect of this study, or if you would like to take part in this study, please contact:

Volunteer Recruitment Coordinator
Centre for Clinical Vaccinology & Tropical Medicine
Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE
Telephone: 01865 611424
Email: [email protected]