The biology of Ross River virus and its cellular receptor

罗斯河病毒(RRV)每年导致多达8000名澳大利亚人患上一种主要的风湿性疾病。这种疾病一开始就很严重，与等待髋关节置换的骨关节炎患者的病情相当。然而，这种疾病通常会在6个月内痊愈。这笔赠款旨在继续我们关于RRV如何以及为什么会导致疾病的研究，并了解为什么每20名RRV感染者中只有1人真正患上疾病。我们认为RRV关节炎是由RRV持续存在于关节组织内的特定白细胞引起的。这笔赠款旨在利用最近的观察结果，即RRV使用一种受体来感染细胞，人类细胞通常使用这种受体与胶原蛋白结合。有了这些新的信息，我们打算揭开RRV如何在患者对病毒产生良好的抗体反应的情况下仍然存在，并确定这种受体的高水平是否易患疾病。这些研究的最终目标是确定这种疾病以及其他由病毒引起的关节炎的潜在新疗法。我们最近还在海豹中发现了一种与轮状病毒有关的新病毒，但幸运的是，它似乎不会对人类的健康构成威胁。然而，我们打算测试这种新病毒是否使用与RRV相同的受体，并开始利用计算机技术探索这些病毒在成功感染人类之前所需的一些突变。

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.