Project: Determining the importance of conserved residues identified throughout the HBV genome on viral replication
Hepatitis B virus (HBV) infection affects over 257 million people worldwide, including 110 million in the Asia-Pacific region and 240,000 Australians. More than 880,000 people die each year directly from HBV related causes, including end-stage liver disease with cirrhosis, liver failure and liver cancer. There is no cure and current treatments are long term, life-long in the vast majority. There is strong consensus among the global HBV community of the need for finite therapies promoting HBV functional cure, and new antiviral targets are required1.
The Revill lab has recently identified novel conserved sequences throughout the HBV genome that are present in multiple HBV strains and disease stages2. These may represent novel antiviral targets, however their importance in the HBV replication cycle is yet to be determined. This project will investigate which of the conserved sequences are most important for HBV replication and thus represent potential antiviral targets. Techniques to be utilised include cell culture, HBV transfection and infection experiments, northern, Southern and western blotting, quantitative serology, siRNA or CRISPR knockdown, PCR and sequencing. This project will generate new knowledge on the importance of HBV sequences in viral replication towards identifying new antiviral targets, thus making an important contribution to global efforts1 to cure HBV infection.
2 Wagner, J. et al. Analysis of hepatitis B virus complete genome haplotype diversity identifies striking sequence conservation across major genotypes and multiple phases of chronic hepatitis B disease. Hepatology, Accepted for publication, June 30, 2020 (2020).
The Revill group’s work is focused on the molecular virology hepatitis B virus (HBV), which is one of the most important human pathogens, infecting 257 million people worldwide, including 239,000 Australians. The lab has a particular interest in the contribution of different HBV genotypes and variants to the striking differences in natural history, disease progression and treatment response observed globally. We also have an interest in determining the role of splicing in HBV-mediated liver cancer. Our studies will provide new insights into the role of spliced HBV variants and HBV genotype in liver disease.