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
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.
Novel Insights Into The Mechanisms Of How Viruses Cause Arthritis-arthralgia
Funder
National Health and Medical Research Council
Funding Amount
$626,459.00
Summary
Many viruses are known to cause arthritis (e.g. HIV, hepatitis viruses, mosquito borne viruses). Symptoms of viral arthritis include joint pain, stiffness, and swelling. The mechanism of disease is poorly understood. We have developed a novel animal model of disease by which to study arthritic disease caused by viral infections. This model provides an excellent opportunity to explore the mechanisms of rheumatic disease in a complete functioning animal and to explore new treatment regimes.
Improving Treatment Strategies For Chronic Alphaviral Arthritic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$643,624.00
Summary
Chikungunya virus and Ross River virus cause epidemics of acute and chronic arthritic disease in humans, which is often poorly managed with current treatments. This grant seeks to understand the mechanisms that give rise to disease in order to identify improved treatment strategies. Both the persistence of viral replication in joint tissues and unnecessary inflammatory responses appear to be important factors driving chronic disease.
Assessment Of Interventions For Controlling Pandemic Influenza And Determining Data Needs To Inform These Assessments
Funder
National Health and Medical Research Council
Funding Amount
$183,040.00
Summary
The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at ri ....The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at risk of being infected. We will compare these control measures by taking due account of the ability and resources available for these interventions, and with regard to the need to maintain essential services. The comparisons will be made using mathematical models that describe the transmission of the infection. All available data and advice from experts will be used to ensure that realistic models are used for the comparisons. We will also use the models to determine the best use of the limited antiviral drugs available, until a vaccine becomes available. We will consider how the control strategy should be changed if a strain develops that is resistant to the antiviral drugs. In addition, we will determine what data need to be collected during the early stages of a pandemic to help us to determine the best use of the antiviral drugs, the best use of a new vaccine and to check on the development of resistance to the antiviral drugs.Read moreRead less
Novel Insights Into The Mechanisms Of How Chikungunya Virus Cause Disease In Humans
Funder
National Health and Medical Research Council
Funding Amount
$554,808.00
Summary
Many of the most dangerous and easily transmitted infectious agents are viruses. The emergence of chikungunya virus globally and the recognition of this pathogen in the aetiology of chronic diseases show the need for a better understanding of how the virus cause disease. The expected outcomes are a better understanding of human alphaviral diseases, with a view to improving prevention and treatment strategies to reduce the disease burden of CHIKV and related viruses.
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.