Hepatitis|Research

• Revill Group

  Peter’s group investigates the role of different HBV genotypes and variants in the HBV life cycle, disease progression and treatment response. This includes the role of splice variants, which his team has shown are predictive of liver cancer.

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  • Lab Team

  

  Professor Peter Revill
  Section Head, Molecular Virology Group, Division of Research and Molecular Development

Current Projects

• Identifying novel biomarkers of HBV treatment response

  Peter is lead investigator on multiple studies interrogating novel biomarkers of treatment response in the setting of antiviral therapy. His team utilises next generation sequencing (Illumina miseq) to sequence the complete HBV genome, to determine the impact of sequence diversity and identify specific mutations associated with adverse or successful treatment. Peter also has an interest in the role of the innate immune response in treatment response, with his team showing that some innate immune responses are predicative of response in the setting of interferon treatment. Importantly, the ability of HBV to down-regulate innate immune responses varies by HBV genotype.

• Novel approaches to HBV cure

  HBV is currently incurable. The HBV X protein is critical for transcription of viral cccDNA, the nuclear form of HBV, which represents a major impediment to HBV cure, as it is not targeted by current antiviral therapies. Peter’s team will utilise cell culture models to investigate the role of the HBx protein in HBV infection, replication and cccDNA stability, to assess the feasibility of HBx as a novel therapeutic target that may lead to HBV cure.

• The emergence of African HBV genotypes in Australian pediatric patients

  Although HBV is mostly transmitted by “mother to baby” worldwide, there have been few studies of HBV in the pediatric setting. HBV chronically infects over 75 million people in Africa where novel genotypes are associated with rapid progression to liver cancer in young males (subtype A1) or reduced vaccine efficacy (genotype E). In collaboration with Associate Professor Winita Hardikar and Dr Liz Bannister at the Royal Children’s Hospital, Peter’s team is investigating the distribution, natural history and molecular virology of African HBV genotypes in a pediatric setting.  

• The role of genotype in HBV pathogenesis

  HBV exists as nine major genotypes, one minor genotype, and over 40 subtypes globally.  HBV natural history, disease progression and treatment response varies markedly for many genotypes and subtypes, for reasons that are unclear. Peter’s team has established an extensive panel of replication competent cDNA clones of all major genotypes and many important subtypes, enabling direct comparison of HBV replication, using cell culture and more recently (in collaboration with Dr Marc Pellegrini at the Walter and Eliza Hall Institute) murine models. He has also established collaborations with international investigators using these clones to interrogate the role of genotype in treatment response.  

• The role of splicing in HBV pathogenesis

  At least 14 different splice-derived RNA or DNA variants have been identified to date in cells or serum obtained from persons with chronic HBV, or from cell cultures transfected with infectious HBV cDNAs. The most frequently detected HBV spliced RNA/DNA is a 1.9 kb molecule termed Sp1, generated by removal of a 1.3 kb intron from the pre-genomic RNA.  We have shown that the presence of spliced variants in patient serum is predictive of liver cancer. Peter is interested to determine the mechanisms by which this occurs and whether spliced variants can be specifically targeted for removal using RNAi.

Lab Team

• Professor Peter Revill

  Section Head, Molecular Virology Group, Division of Research and Molecular Development
• Tina Sozzi

  Senior Research Assistant
• Dr Liz Bannister

  PhD candidate
• Dr Zina Valaydon

  PhD candidate
• Miss Thao Huynh

  Honours student
• Mr Hugh Mason

  Research Assistant

• Bowden Group

  Scott’s laboratory is the State Reference Laboratory for molecular testing of the hepatitis viruses and has been involved in outbreak investigation of hepatitis A, B, C and E for the Victorian Department of Health, as well as for other Australian states.

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• Cowie Group

  Ben’s group focuses on viral hepatitis epidemiological research. The team undertakes a broad range of activities supporting local, national and global control of viral hepatitis, through surveillance, treatment and prevention initiatives, and training and regional capacity building. 

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  Other work areas include:Public Health

  

  Professor Benjamin Cowie
  Director, WHO Collaborating Centre for Viral Hepatitis

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• Locarnini Group

  The current major research interests of Stephen’s group includes viral hepatitis and antiviral chemotherapy with an emphasis on the basic virology of hepatitis B virus, the molecular pathogenesis of hepatitis, as well as prevention and public health control measures.

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• Nicholson Group

  Suellen's group fulfills a dual mission of providing a technically first class, reliable diagnostic, reference and public health service to the healthcare system, and being an innovative, adaptable, forward-looking component of the scientific community and a valued collaborator in research projects, not just in Victoria, but nationally and in the region.

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  Other work areas include:HIV

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• Walsh Group

  Renae’s group studies key HBV proteins to predict clinical response during chronic disease towards understanding the interaction with/recognition by the host antibody response to clear infection, and how the antibody response might be enhanced to promote viral clearance and cure. 

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