Clearing Chronic Infectious Diseases – Enhancing Host Immune Effector Function
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Chronic infections produced by pathogens such as HIV, overwhelm our immune system leading to an exhausted state where cells responsible for the clearance of invading microorganisms are unable to respond effectively. We have recently identified a highly promising therapeutic target that enhances immune effector function. We seek to understand the underlying mechanism, and to explore the therapeutic potential of this approach for the treatment of a broad range of pathogens, including those respons ....Chronic infections produced by pathogens such as HIV, overwhelm our immune system leading to an exhausted state where cells responsible for the clearance of invading microorganisms are unable to respond effectively. We have recently identified a highly promising therapeutic target that enhances immune effector function. We seek to understand the underlying mechanism, and to explore the therapeutic potential of this approach for the treatment of a broad range of pathogens, including those responsible for chronic disease.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
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.
I am a molecular virologist researching the host response to hepatitis C virus (HCV) infection with the aim of understanding how the liver clears HCV infection. An understanding of this process will hopefully lead to novel antiviral strategies to combat not only HCV but a broad range of other viral infections.
Hepatitis C Virus infects 3% of the world's population causing recurring liver disease, cirrhosis and hepatocellular carcinoma. To infect a liver cell, the viral glycoproteins attach to cell surface molecules wher they are activated to mediate merger of the viral and cellular membranes. This project grant will explore how the viral glycopropteins become activated and obtain essential structural information on the viral glycoproteins. These studies will help us to design antiviral agents.
Roles Of The Hepatitis C Virus Glycoprotein E2 Variable Regions In Virus Entry, Immunogenicity And Immune Evasion.
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Hepatitis C Virus infects 200 million people world-wide with over 200,000 Australians infected with the disease. This project will examine how the surface proteins of HCV change their shape to evade antibody responses and how this effects the outcome of infection. We will further characterize a vaccine that elicits protective immunity to HCV to identify the optimal formulation for clinical trials.
The Role Of CXCR3 Chemokines In Hepatitis C And Other Forms Of Viral Hepatitis
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 10-20 years. This liver disease is primarily a result of the host immune response to liver cells (hepatocytes) infected with HCV. As part of this immune response there in an increase in the number of immune cells that infiltrate the liver. To date we do not fully understand the mechanims that attract these cells to the liver but a class of molecules called chemokines is the ....The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 10-20 years. This liver disease is primarily a result of the host immune response to liver cells (hepatocytes) infected with HCV. As part of this immune response there in an increase in the number of immune cells that infiltrate the liver. To date we do not fully understand the mechanims that attract these cells to the liver but a class of molecules called chemokines is the most likely candidate. Thus a greater understanding of the chemokines expressed in the liver, their modulation and role in attracting immune cells to the liver in HCV-related liver disease will help us understand the basic mechanisms of liver disease with the possibility of development of novel therapeutic strategies. In pilot studies we have shown that the chemokine interferon-inducible T cell alpha chemoattractant (I-TAC) is significantly increased in the liver of persons infected with HCV. I-TAC is a member of the CXCR3 ligand chemokine family that attracts lymphocytes to sites of inflammation and as such may play an important role in hepatitis C. We have also shown that hepatocytes express I-TAC and that HCV can upregulate expression of I-TAC in a laboratory model of HCV replication. This proposal plans to determine the molecular mechanisms of I-TAC expression in response to HCV replication and to investigate if I-TAC expression is unique for hepatits C or a general feature of viral infections of the liver. We also plan to determine the the role of I-TAC and other CXCR3 ligand family members in a mouse model of viral hepatitis through the use of CXCR3 ligand antagonists. These experiments will enhance or knowledge of the role of the CXCR3 ligands in hepatitis C and viral hepatitis in general.Read moreRead less