The biology of Ross River virus and its cellular receptor

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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.