Ross River virus (RRV), the most common cause of mosquito-borne disease in Australia, results in a debilitating arthritis in humans. The clinical manifestations typically presented include maculopapular rash, fever, myalgia and polyarthralgia. Viraemia usually clears within a week after infection and it is unclear how patients still experience long-term symptoms such as myalgia and polyarthralgia after recovery from the initial infection1. Another alphavirus, Barmah Forest virus (BFV), causes similar disease in infected humans though rash is more commonly observed2 BFV infection is typically seen as a milder form of RRV infections and is often under-reported or misdiagnosed as RRV3. Many mouse model studies have demonstrated that RRV is able to replicate to high titres in bones, joints and skeletal muscle associated tissues4. Furthermore, it has been shown that RRV RNA can be detected in the synovium extracted from the joints of RRV disease patients five-weeks post initial clinical presentation5.
To determine if persisting levels of infectious virus and/or viral genome is a contributing factor to alphavirus-induced chronic disease, we aimed to determine the cell types which are permissive to RRV and BFV infection and demonstrate their potential as reservoirs for long-term viral replication and/or maintenance of viral RNA. To investigate this, we are conducting long-term RRV and BFV infections using cell types present in joints and surrounding tissues such as chondrocytes, macrophages, myocytes, osteoclasts and osteoblasts. We will also characterise the inflammatory response during long-term RRV and BFV infections by gene expression of host factors involved in innate immunity. Preliminary data shows that infectious RRV virus and viral RNA has been detected in RRV-infected human primary chondrocytes up to 11 and 63 days post-infection respectively. Collectively, the data produced will for the first time demonstrate that RRV and/or its genome can persist in cells from joints and muscle.