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.
A vaccine for hepatitis C virus (HCV) is not yet available. Immune responses that are able to protect against infection are possible, making the production of a vaccine a realistic goal. We have produced a unique HCV vaccine and are now poised to test our vaccine in novel humanised animal models. Our research will allow us to determine the immune responses responsible for providing protection against HCV. Our data will be highly significant for future HCV vaccine studies in humans.
Improved Health Outcomes For People Living With HIV
Funder
National Health and Medical Research Council
Funding Amount
$560,284.00
Summary
Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected wi ....Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected with hepatitis B virus (HBV)Read moreRead less
Hepatitis C virus is a major medical problem in Australia and many other parts of the world. The viruses causes a persistent infection in most infected individuals that results in serious liver disease and liver cancer in a proportion of patients. Treatment is only possible for a small percentage of patients and many patients are infected with viruses which are resistant to the best contemporary treatment regimens. The aim of this project is to develop systems which will result in the assembly o ....Hepatitis C virus is a major medical problem in Australia and many other parts of the world. The viruses causes a persistent infection in most infected individuals that results in serious liver disease and liver cancer in a proportion of patients. Treatment is only possible for a small percentage of patients and many patients are infected with viruses which are resistant to the best contemporary treatment regimens. The aim of this project is to develop systems which will result in the assembly of virus particles which can be used to examine the efficacy of potential antiviral agents, either in the test tube or by infecting an animal model. In particular, we will examine the contribution of a small viral protein, p7, on virus assembly and secretion from the infected cell. Recent data suggests that p7 can function to help release virus from the infected cell and a number of inhibitors of p7 function have been described. We will then use the systems which we develop to determine if these inhibitors can inhibit virus replication in the test tube and in animal models.Read moreRead less
UNDERSTANDING HEPATITIS C VIRUS-SPECIFIC T CELL TOLERANCE
Funder
National Health and Medical Research Council
Funding Amount
$429,710.00
Summary
Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have ....Most individuals who are infected with hepatitis C virus (HCV) develop a persistent infection that is lifelong and are at risk of developing serious liver disease, including liver cancer. The evidence suggests that an inadequate immune response is responsible for the inability of the patient to resolve the infection, but it is not clear which stage of the immunological cascade might be targeted. In this project, we will test the hypothesis that HCV antigen induce supressor T cells This will have the effect of inhibiting the immune response and result in the outcome that we currently recognise as persistent HCV infection.Read moreRead less
A New Insight Into Hepatitis B Infection:the HBV Fusion Peptide
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Three hundred and fifty million people worldwide and 250,000 in Australia are chronically infected with hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current therapies are inadequate. New antiviral treatments requiring the identification of new antiviral targets are needed to combat the disease but a major obstacle to the study of HBV is the lack of a cell culture system. As a result n ....Three hundred and fifty million people worldwide and 250,000 in Australia are chronically infected with hepatitis B virus (HBV). Without intervention, one third will die as a direct result of this infection through cirrhosis, liver failure and liver cancer, but current therapies are inadequate. New antiviral treatments requiring the identification of new antiviral targets are needed to combat the disease but a major obstacle to the study of HBV is the lack of a cell culture system. As a result nothing is known about how HBV enter and fuses with the host liver cell but we have made significant progress with the identification of the entry and fusion events of the related duck hepatitis B virus, using the duck infection model. This knowledge is now ready for application to the medically important HBV by use of primary human liver cells and the techniques developed in the duck hepatitis B virus model.Read moreRead less
Imaging The Hepatitis C Virus Life Cycle In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may unco ....Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may uncover novel therapeutic strategies to combat HCV.Read moreRead less
Use Of Mouse Models To Study Mechanisms Of Pathology In Viral Exacerbations Of COPD
Funder
National Health and Medical Research Council
Funding Amount
$411,960.00
Summary
We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our re ....We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our research is chronic obstructive pulmonary disease. COPD is a serious lung disease which generally occurs in people who have smoked for many years. However, many COPD patients stopped smoking many years ago. COPD patients are especialy at risk of serious outcomes if they get a respiratory infection (known as an acute COPD exacerbation) and patients with COPD exacerbations use a lot of health care resources. There are no effective drugs to prevent or treat COPD exacerbations. We are currently using a mouse model of smoke exposure and virus infection to do this research, which is a much faster and more ethical approach than using humans in research. We believe that we will get a better understanding of how smoke affects the immune response to infection. This is likely to contribute to the development of better drugs for COPD exacerbations and other types of smoking related lung disease.Read moreRead less
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.