Identification Of Novel HCV-specific B Cell Epitopes Which Induce Broad Neutralising Antibodies
Funder
National Health and Medical Research Council
Funding Amount
$482,480.00
Summary
This research project will study humans who have been exposed to multiple Hepatitis C virus infections. We will be examining their immune response with the aim to identify subjects with antibodies that are able to neutralise a diverse range of hepatitis C virus variants. These antibodies will be used to identify novel targets for a vaccine directed against Hepatitis C virus.
Most individuals infected with hepatitis C virus (HCV) develop progressive liver disease. A vaccine is urgently needed, and needs to mimic the immune responses seen in the minority of individuals who clear infection. However, there are large gaps in our understanding of these responses as most acute infections cause no illness and pass unnoticed. This project will fill these gaps by detailed immunological and virological analysis of a large group of subjects with early infection.
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.
Characterization Of ARL6IP5 In Hepatitis C-related Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,283.00
Summary
The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hep ....The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hepatitis C leads to cancer.Read moreRead less
microRNAs (miRNAs) constitute a novel mechanism used by cells and viruses to regulate gene expression. Studies carried out in non-human primates demonstrated great potential for miRNA-inhibiting drugs as novel antiviral agents against hepatitis C virus infection. By characterising how miRNAs control the antiviral state, we will gain new insights into how miRNA-modulating drugs could present novel strategies to treat viral infections.
Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Influenza A Virus PB1-F2 Protein: A Putative Virulence Factor And Initiator Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$474,718.00
Summary
Influenza virus produces a protein of undefined function called PB1-F2. Infection of mice with virus expressing PB1-F2 from virulent strains causes severe lung inflammation, while PB1-F2 from milder seasonal viruses does not. We will examine how PB1-F2 influences virulence of human influenza in the ferret, which exhibits the same illness as humans. This work will help understand the disease severity of newly evolved influenza viruses of humans and the role of PB1-F2 in mediating this.