Ross River virus: Molecular and cellular aspects of disease pathogenesis

Ross River virus (RRV) is a mosquito-borne alphavirus indigenous to Australia and the Western Pacific region and is responsible for several thousand cases of human RRV disease (RRVD) per annum. The disease primarily involves polyarthritis/arthralgia, with many patients also presenting with rash, myalgia, fever, and/or lethargy. The symptoms can be debilitating at onset, but they usually resolve within 3-6 months. Recent insights into the RRV-host relationship, associated pathology, and molecular biology of infection have generated a number of potential avenues for improved treatment. Although vaccine development has been proposed, the small market size and potential for antibody-dependent enhancement (ADE) of disease make this approach unattractive. Recent insights into the molecular basis of RRV-ADE and the virus's ability to manipulate host inflammatory and immune responses create potential new opportunities for therapeutic invention. Such interventions should overcome virus-induced dysregulation of protective host responses to promote viral clearance and/or ameliorate inflammatory immunopathology.