Characterisation Of Anti-HBs Responses In Patients Undergoing Functional Hepatitis B Cure: Implication For Future Therapies
Funder
National Health and Medical Research Council
Funding Amount
$723,649.00
Summary
The hepatitis B virus causes liver cirrhosis and liver cancer. There is no cure for hepatitis B. However, a small number of patients can naturally rid themselves of the virus. We have identified 14 of these individuals and discovered that they have a unique immune response that is responsible for these “natural” cures. We plan to characterise this immune response and turn it into a therapeutic vaccine which can be used to cure patients who are still chronically infected.
Chronic Active Viral Persistence Versus Host Immune Mediated Pathology: An Analysis And Manipulation Of The Balance.
Funder
National Health and Medical Research Council
Funding Amount
$418,658.00
Summary
Our robust ability to mount an immune response and clear infections is tempered by the possibility of promoting autoimmunity. Several host genes regulate immunity. Viruses like HIV have exploited these to abrogate antiviral immunity. This project attempts to define host factors that promote chronic infection. This will be extremely valuable in understanding the vulnerabilities of our immune system and provide an insight into how we can treat chronic infections.
Worldwide >360 million people have chronic hepatitis B virus (HBV) infection that imparts a 25% lifetime risk of death due to serious liver disease. Current therapies for chronic HBV reduce levels of virus replication but fail to target the stable, nuclear episome, covalently closed circular DNA (cccDNA). The current study will determine what is required to eliminate cccDNA and how current therapies for chronic HBV infection should be modified to achieve this aim.
Novel Bioinformatic Methods To Determine The Link Between Genomic Complexity Of Hepatitis Viruses And Liver Disease Phenotypes
Funder
National Health and Medical Research Council
Funding Amount
$605,859.00
Summary
Bioinformatics is a discipline concerned with the study of how information is stored and used in biological systems. Here we develop bioinformatic tools to study how hepatitis viruses evolve during an infection and how these infections cause severe liver diseases.
Towards A Functional Cure For HBV: Exploiting Lessons From HBV-HIV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$913,551.00
Summary
Hepatitis B virus (HBV) infection can be treated, but therapy is usually lifelong and has side effects, so a cure for HBV is very important. We work closely with colleagues in Asia where both HBV and HIV are common so this provides a unique opportunity to study HBV. We will investigate how an effective immune response against the 2 main HBV proteins is developed. If we can understand how the immune response works against HBV, this could be used to develop new therapies to develop a cure for HBV
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
Long Term Persistence Of HIV In The Liver And The Clinical Impact On HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$1,393,245.00
Summary
This grant will address a major question in HIV cure research - the role of the liver as an HIV reservoir and the impact of HIV persistence in HIV-infected patients on suppressive antiretroviral therapy (ART) on liver disease, in the setting of HIV-HBV co-infection. We will trial a novel intervention to reduce HIV infection of the liver that could potentially reduce chronic liver disease in this setting.
Morbidity and mortality secondary to liver disease is greatly increased in people co-infected with HIV and HBV compared to those infected with HBV alone. Mortality remains elevated even after treating both viruses. This project will investigate the mechanism of how HIV accelerates liver disease in patients co-infected with HBV. We hypothesize that this occurs by combined effects of HIV and HBV on inflammation in the liver. These studies could potentially lead to new treatments for liver disease.
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.