Novel Insights Into The Mechanisms Of How Viruses Cause Arthritis/Arthralgia
Funder
National Health and Medical Research Council
Funding Amount
$78,187.00
Summary
Viruses cause many diseases today and new viruses emerge to post threats to future health and well being. The proposed work investigates how viruses cause disease in people, particularly how viral infections can lead to arthritis or muscle pain. This understanding will be used in the development of new prevention strategies and treatments.
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
New mathematical and statistical methods that inform the control of infectious disease outbreaks. Emerging infectious diseases are an ever-present threat to our community, as highlighted by the recent SARS epidemic and current fears concerning avian influenza. The research proposed by this project will help policy makers implement effective border control and outbreak control against a variety of emerging and re-emerging infectious diseases, including SARS, influenza and the deliberate release o ....New mathematical and statistical methods that inform the control of infectious disease outbreaks. Emerging infectious diseases are an ever-present threat to our community, as highlighted by the recent SARS epidemic and current fears concerning avian influenza. The research proposed by this project will help policy makers implement effective border control and outbreak control against a variety of emerging and re-emerging infectious diseases, including SARS, influenza and the deliberate release of an infectious disease such as smallpox. The project will enhance preparedness through a better understanding of the relative merits of different control strategies, and provide new methodology that can dynamically guide border and outbreak control in the midst of an outbreak by making effective use of data. Read moreRead less
Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucida ....Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucidate whether there is any association between RRV strain and the severity of human disease. It will also identify viral markers that could assist public health officials in determining likely disease outcomes of outbreaks and could provide new avenues for the design of antiviral strategies.Read moreRead less
Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is ....Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is an association between RRV strain and the severity of disease and if there are human factors that affect the seriousness of symptoms. Knowledge of both of these could provide new avenues for the design of prevention and treatment strategies.Read moreRead less
A National Population-based Study Of Rheumatic Heart Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$877,826.00
Summary
Whilst overall a rare disease, Indigenous peoples have disproportionately high rates of rheumatic heart disease (RHD). This study explores the prevalence and distribution of RHD in pregnancy in Australia and New Zealand. It details current management, diagnostic and referral process and risk factors. Key attributes of culturally safe models of care for RHD in pregnancy are explored, particularly as they relate to Indigenous women. Findings will inform policy, guidelines and education resources.