Ross River virus (RRV) is a common mosquito-borne alphavirus that causes debilitating arthritis in thousands of Australians annually1. The clinical manifestations typically presented include maculopapular rash, fever, myalgia and polyarthralgia. Interestingly, 5-50% of patients experience long-term joint and muscle pain after recovery even though viraemia usually clears one week after infection1,2. Many mouse studies have demonstrated that RRV can replicate to high titres in bones, joints and skeletal muscle associated tissues3. Furthermore, RRV RNA has been detected in synovium of RRV disease patients up to five-weeks post initial clinical presentation4. Our goal is to determine if persisting levels of infectious virus and/or viral genome present in the joints contributes to alphavirus-induced chronic disease.
In this study, we will identify the cell types that can harbour long-term RRV viral replication and/or maintenance of viral RNA. Cells present in joint-associated tissues such as chondrocytes, macrophages, myocytes, osteoclasts and osteoblasts will be infected with RRV for up to 120 days. Viral genome transcription and/or host inflammatory responses will be measured every 1-2 weeks by gene expression analysis.
Preliminary data has shown that infectious RRV virus and viral RNA can be detected in human primary chondrocytes up to 11 and 122 days post-infection respectively. Additionally, we found changes in gene expression of several key soluble factors associated with disease pathogenesis (IL-6, MCP-1, TNF-a, etc.). Collectively, the data produced will, for the first time, demonstrate the persistence of RRV and/or its genome in cells of joints.