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
ARC Centre of Excellence in Quantum Biotechnology. ARC Centre of Excellence in Quantum Biotechnology. The ARC Centre of Excellence in Quantum Biotechnology aims to develop paradigm-shifting quantum technologies to observe biological processes and transform our understanding of life. It seeks to create technologies that go far beyond what is possible today, from portable brain imagers to super-fast single protein sensors, and to use them to unravel key problems including how enzymes catalyse reac ....ARC Centre of Excellence in Quantum Biotechnology. ARC Centre of Excellence in Quantum Biotechnology. The ARC Centre of Excellence in Quantum Biotechnology aims to develop paradigm-shifting quantum technologies to observe biological processes and transform our understanding of life. It seeks to create technologies that go far beyond what is possible today, from portable brain imagers to super-fast single protein sensors, and to use them to unravel key problems including how enzymes catalyse reactions and how higher brain function emerges from networks of neurons. By building a diverse, multidisciplinary, and industry-engaged ecosystem, the Centre means to develop our future leaders at the interface of quantum science and biology and drive Australian innovation across manufacturing, energy, agriculture, health, and national security.Read moreRead less