Glycotherapeutics; A New Class Of Treatment For Alphavirus-induced Musculoskeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$449,868.00
Summary
The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. Currently there is no licenced specific treatment for alphavirus disease and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. This grant looks at the potential of pentosan polysulfate as a promising drug-repurposing candidate for the treatment of alphavirus-induced arthritis.
The Role Of Innate Inflammatory Responses In Viral Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$782,514.00
Summary
Viruses are known to cause arthritis (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 and human cell culture models by which to study disease caused by viral infections. This models provide an excellent opportunity to explore the mechanisms of rheumatic disease in a functioning animal and to explore new treatment regimes.
Inhibition Of Interferon-?/? Induction By Ross River Virus
Funder
National Health and Medical Research Council
Funding Amount
$589,664.00
Summary
Ross River virus is a mosquito-borne virus that causes arthritis in the joints of many people infected. This project will look at the early interactions of a virulent virus with the mammalian host that appear to enable the virus to replicate and spread in the host and thereby cause disease. These interactions are with the host interferon protein which the virus has developed the ability to inhibit. The effect of the invading virus on the host's interferon system, part of the immune system, will ....Ross River virus is a mosquito-borne virus that causes arthritis in the joints of many people infected. This project will look at the early interactions of a virulent virus with the mammalian host that appear to enable the virus to replicate and spread in the host and thereby cause disease. These interactions are with the host interferon protein which the virus has developed the ability to inhibit. The effect of the invading virus on the host's interferon system, part of the immune system, will be examined.Read moreRead less
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
The Biology Of Ross River Virus And Its Cellular Receptor
Funder
National Health and Medical Research Council
Funding Amount
$252,750.00
Summary
Ross River virus (RRV) causes a principally rheumatic disease in up to 8000 Australian annually. The disease is severe at onset comparable to that suffered by patients with osteoarthritis awaiting hip replacement. However, the disease usually resolves within 6 months. This grant intends to continue our studies on how and why RRV causes disease and develop an understanding of why only 1 person in 20 infected with RRV actually develops disease. We believe RRV arthritis is cause by RRV persisting i ....Ross River virus (RRV) causes a principally rheumatic disease in up to 8000 Australian annually. The disease is severe at onset comparable to that suffered by patients with osteoarthritis awaiting hip replacement. However, the disease usually resolves within 6 months. This grant intends to continue our studies on how and why RRV causes disease and develop an understanding of why only 1 person in 20 infected with RRV actually develops disease. We believe RRV arthritis is cause by RRV persisting in specific white blood cells residing within joint tissues. The grant intends to exploit the recent observation that to infect cells RRV uses a receptor, which human cells normally use to bind to collagen. Armed with this new information we intend to unravel how RRV can persist despite the patient making good antibody responses against the virus, and determine whether high levels of this receptor predispose to disease. The ultimate goal for these studies is the identification of potential new treatments for this and perhaps other arthritic diseases caused by viruses. We have also recently identified a new virus in seals that is related to RRV, but fortunately appears not to pose a health threat to humans. However, we intend to test whether this new virus uses the same receptor as RRV and begin to explore using computer technology some of mutations these viruses would need before they could successfully infect humans.Read moreRead less
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.
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.
Mosquito-borne alphaviruses such as Ross River and chikungunya viruses cause widespread epidemics and exert extreme pressure on the public health systems of affected regions. Alphaviruses spreads to joints and triggers a severe disease in those affected. There are no effective treatments or vaccines. The project will investigate virus-host interaction at the bite site. The outcome will be new knowledge to treat infection at the mosquito bite site to prevent joint disease.