Mechanisms Of Immune Modulation By Varicella Zoster Virus During Cutaneous Infections
Funder
National Health and Medical Research Council
Funding Amount
$570,446.00
Summary
Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes two skin diseases: chicken pox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease. Shingles aff ....Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes two skin diseases: chicken pox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease. Shingles affects many elderly individuals and a major complication is prolonged severe pain or post-herpetic neuralgia (PHN), which can be severely debilitating and often requires follow-up medical care for months or even years after the initial attack. Despite its significant impact on the community, little is known about how this virus functions and causes disease. This project aims to improve our understanding of how VZV infection of the skin affects the function of specialised skin cells in order to provide novel information for the development of therapies aimed at lessening the impact of VZV disease on the community. This project has three main components: (1) To determine what the differences are in the types of immune cells present in infected skin from chicken pox and shingles sufferers. (2) To assess the impact of VZV infection on the ability of specialised immune cells (called dendritic cells) to function properly (3) To identify which parts of the virus (called genes) code for functions that interfere with the proper function of specialised immune cells (dendritic cells)Read moreRead less
Profiling The Specificity Of The Neutralizing Antibody Response In People Who Have Long Term Protection From Developing Chronic HCV
Funder
National Health and Medical Research Council
Funding Amount
$372,972.00
Summary
Hepatitis C causes chronic liver disease in over 150 million people world-wide. In this study we will determine the qualities of the immune response that protect individuals from HCV infection and reinfection. The outcomes of this study will provide a pathway for the development of vaccines that elicit protective immune signatures.
The Role Of Rip3 And Caspase 8 In Necroptosis And Apoptosis During Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Programmed cell death can be beneficial or detrimental depending on circumstances. This delicate balance is most obvious during an infection. The host tries to limit the spread of a pathogen by initiating programmed death in infected cells but excessive death particularly in uninfected cells is catastrophic. It is essential to have a thorough understanding of the interplay between cell death mechanisms so we can overt pathological outcomes and this is the focus of our research.
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.
I am a virologist carrying out research to determine the mechanisms underlying rotavirus cellular tropism and the pathogenesis of rotavirus disease. Rotavirus is the major cause of infantile gastroenteritis worldwide. I am combining the expertise of my group in rotavirus biology with the power of inter-disciplinary collaborations in the areas of sugar chemistry, cell biology, structural biology and diabetes to expand understanding in these areas. Novel treatments and improvements in rotavirus va ....I am a virologist carrying out research to determine the mechanisms underlying rotavirus cellular tropism and the pathogenesis of rotavirus disease. Rotavirus is the major cause of infantile gastroenteritis worldwide. I am combining the expertise of my group in rotavirus biology with the power of inter-disciplinary collaborations in the areas of sugar chemistry, cell biology, structural biology and diabetes to expand understanding in these areas. Novel treatments and improvements in rotavirus vaccines are the long term goal of our research.Read moreRead less
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.
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.
Characterization Of Neutralizing Antibody Responses In HCV Infected Individuals.
Funder
National Health and Medical Research Council
Funding Amount
$478,076.00
Summary
Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attri ....Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attributed to the development of a strong cellular immune response and antibody is belived to play a monir role in achieving viral clearance. However, measurememnt of antibody responses in HCV infected pateints is routinely performed using conventional diagnostic tests that do not measure antibody that can help neutralize and clear virus. We have developed an assay that accurately measures the level of NAb in patient sera. We have found that chronically infected patients have broadly reactive neutralizing antibodies but that patients who clear virus, naturally or through treatment do not have broadly reactive neutralizing antibodies. Possibly explaining this phenomenon is that early during infection, antibody is frequently specific only to the infecting virus therefore to detect neutralizing antibodies, homologous viral sequences must be examined. In addition, we have found evidence that HCV can evade neutralzing antibodies through masking of sites to which antibodies bind. We propose to explore whether acutely infected patients develop NAb to autologous viral sequences, and how do these viral sequences and the antibody titre change throughout the course of infection and treatment. We also plan to determine the mechanism of neutralization resistance through the use of mutagenesis of resistant HCV glycoproteins. These studies are aimed at gaining a thorough understanding of the true role of antibody in HCV infection and its influence on viral evolution.Read moreRead less
Detailed Investigation Of The Humoral Immune Response To HCV To Identify Diagnostic And Prognostic Serological Markers
Funder
National Health and Medical Research Council
Funding Amount
$387,466.00
Summary
The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the d ....The prevalence of Hepatitis C in Australia has been estimated at 242 000 people with 80% of infections acquired as a result of infection drug use. The currently available assays can be used to reliably determine the prevalence of Hepatitis C infection but provide no information regarding the incidence of infection. By thoroughly investigating the immune response generated by individuals infected with Hepatitis C we intend to identify interactions which can be used to differientiate between the different stages of infection. The expected outcomes of this study include the identification of a marker of recent Hepatitis C infection. This will permit accurate epidemiological monitoring of Hepatitis C, better design of programs to control the spread, trace outbreaks and manage treatment programs. The identification of a marker capable of predicting the clinical outcome of infection would be invaluable to clinicians, because following acute infection with Hepatitis C, 20 to 30% of individuals will resolve their infection without the need for therapeutic intervention. The information obtained in this study will also lead to a better interpretation of diagnostic laboratory findings, improving our ability to provide clear and accurate reports to blood donors and consequently enhance the Australian blood supply in terms of safety and donor retention.Read moreRead less
Rotavirus is the main cause of severe diarrhoea in children worldwide. In this project, we aim to understand the nature of the first-line immune response to rotavirus in the gut, and elucidate how RV counteracts this response to promote infection. These studies will increase our understanding of how rotavirus causes disease, and facilitate the choice of rotavirus targets for drug development and improved vaccines.