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
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