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
ANTIVIRAL DRUG RESISTANT HBV: PATHOGENIC AND ONCOGENIC SIGNIFICANCE OF THE ALTERED VIRAL ENVELOPE
Funder
National Health and Medical Research Council
Funding Amount
$509,284.00
Summary
We aim to investigate the consequences of long-term therapy for hepatitis B on liver cancer progression. We propose that antiviral therapy is associated with persistent expression and accumulation of potentially oncogenic surface proteins in the liver. This can dramatically alter the viral lifecycle, particularly the HBsAg secretion pathway, which can cause serious effects in the host hepatocyte biology, including promoting pathways to tumour formation.
Protein Topogenesis And The Assembly/disassembly Of The Enveloped Hepatitis B Virus.
Funder
National Health and Medical Research Council
Funding Amount
$197,884.00
Summary
An estimated 350 million people worldwide, and 250,000 in Australia, are chronically infected with the 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 treatments are inadequate. A major obstacle to the study of this virus is the lack of a cell culture infection system. We have used the duck hepatitis B virus (DHBV) model to study the events leading up to assembly of the virus in ....An estimated 350 million people worldwide, and 250,000 in Australia, are chronically infected with the 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 treatments are inadequate. A major obstacle to the study of this virus is the lack of a cell culture infection system. We have used the duck hepatitis B virus (DHBV) model to study the events leading up to assembly of the virus in a way which prepares the viral envelope or outer coat for its foray into a new host cell. The project will examine the specific interactions of two proteins, the large and the small envelope protein, in addition to a third envelope protein we have recently discovered, which together make up the viral envelope. This will reveal which envelope components are required to make up the specific structures known to be essential for the disruption of the host cell membrane and subsequent entry of the virus to a new cell. An understanding of the changes that occur to the viral envelope upon entry will enable development of strategies for the inhibition or blocking of this change, thus identifying targets for the development of new antiviral agents. Because HBV is just one of many viruses which have an envelope, all of which must enter the cell in some way, our studies of HBV will also provide new clues with respect to the replication of other viruses such as measles, influenza and HIV. A related part of the study will examine the orientation of the large envelope protein within the virus particle and how it changes its orientation to assume its many important functional roles, in the late stages of particle assembly. Expanding on our finding that the small protein is essential to the orientation of the large protein, this study will reveal the mechanism of a unique method of protein transport which may have wider implications in cell biology.Read moreRead less
Suppression Of Immune Toll-like Receptor (TLR) Signaling By Hepatitis B E Antigen (HBeAg)
Funder
National Health and Medical Research Council
Funding Amount
$542,320.00
Summary
Hepatitis B virus (HBV) infection is a major world-wide health problem, which the current treatment strategies are not ideal. Therefore understanding how HBV inteacts with the immune system is of critical importance to developing intervention strategies to promote better health outcomes. This grant will develop our novel findings that a protein produced by HBV 'blinds' the host immune system by producing a protein that blocks the innate immune response to allow HBV to replicate unchallenged.
There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this proj ....There are a number of patients throughout Victoria that are co-infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV). These patients are currently being treated for HIV with multiple antiviral drugs and are living for longer periods. Lamivudine is one of the drugs in the HIV antiviral treatment regime. This antiviral is also effective against hepatitis B virus and is the only licensed nucleoside analogue that is used in the treatment of hepatitis. The aim of this project is to investigate the liver disease caused by HBV in co-infected patients and the development of antiviral resistance due to the long-term treatment with lamivudine. We will develop a data base to monitor virological, biochemical and histological parameters for each of these co-infected patients. We will collate all information on these patients that are attending these various centres. This data base will be essential for monitoring the disease in patients with a poor immune system versus patients with a normal immune system. The HBV virus isolated from these patients will be characterised by sequence analysis. The sequence analysis of these viruses will be compared before and after treatment to determine any resistance markers that have developed. These resistant markers will be copied into an infectious clone using specialised molecular techniques. Clones containing these resistant markers will be analysed in the laboratory to determine the antiviral sensitivity to lamivudine and a number of new drugs against hepatitis B virus. This information will be important in treating patients that are co-infected with HBV and HIV and have already developed resistance to lamivudine.Read moreRead less