Ross River virus (RRV) is a mosquito-borne alphavirus and the aetiological agent of epidemic polyarthritis (EPA). Arthropod borne-Alphaviruses that are related to RRV, such as Chikungunya virus, Sindbis virus and Barmah Forest virus, are usually associated with epidemics of infectious arthritides in different parts of the world. In humans, RRV-induced disease symptoms include fever, rash, myalgia and pain and stiffness of the joints. Muscle and joint pain are the most debilitating symptoms in RRV patients and the best treatment available is non-steroidal anti-inflammatory drugs (NSAID). Previous studies in mice have demonstrated that RRV infection results in inflammation of skeletal muscle and joints and that macrophages play a primary role in disease. The present study was carried out to further elucidate the underlying mechanisms mediating RRV-induced muscle and joint pathology. Previous studies have reported that encephalitic alphaviruses trigger apoptosis of brain cells in mice and that blocking apoptosis reduces mortality rates. In the present study, the ability of RRV to induce muscle apoptosis was investigated in vitro, using a murine myoblast cell line (C1C12), and in vivo, using a mouse model of RRV disease. RRV-infected C1C12 myofibres displayed an array of morphological and biochemical makers of apoptosis. Apoptosis was also observed in the skeletal muscle of RRV-infected C57BL/6J mice. Blocking apoptosis by general caspase inhibition resulted in milder disease symptoms, reduced myofibre damage and decreased inflammation of muscle and joint tissues. The total number of cell infiltrates as well as the number of macrophages infiltrating muscle was significantly reduced by the treatment with a caspase inhibitor. The effects of RRV infection on the skeletal system were also investigated. Primary human osteoblast cells were infected with RRV and monitored for viral-induced cytopathic effect. Osteoblasts supported rapid virus growth and, by 48 hours after infection, succumbed to viral-induced necrosis. In addition, histological examination of bone tissue from RRV-infected C57BL/6J mice showed clear evidence of bone resorption. Tibias from infected mice showed an increased number of activated osteoclasts, a reduction in bone density and thinning of cortical bone. The expression of host factors involved in inflammatory responses and bone remodelling was studied in RRV-infected myofibres and osteoblast cell cultures and in the muscle and joint tissues from infected mice. RRV-infected muscle cells and tissue showed elevated mRNA levels for the chemokines CCL-2, CCL3, CCL5 and CXCL1, all of which are known to mediate the migration of monocytic cells. With the exception of CXCL1, these chemokines were also found to be up-regulated in RRV-infected osteoblast cultures and in joint tissues from infected mice. Muscle and joint tissue from infected mice also showed elevated mRNA levels for type I and type II interferons, TNF- and NOS2. In addition, joint tissues from infected animals contained high levels of IL-6 and IL-1, two cytokines known to mediate bone remodelling. Finally, the therapeutic potential of the drug bindarit was investigated using the mouse model of RRV disease. Bindarit is a known inhibitor of CCL-2 and TNF- and has been found to prevent protein denaturation. Treatment with bindarit resulted in mice developing milder disease symptoms, reduced muscle damage and decreased inflammation of muscle and joint tissues. In particular, bindarit significantly reduced macrophage infiltration into skeletal muscle tissue. This thesis has contributed to the understanding of RRV pathogenesis. It has identified novel mechanisms of RRV-induced muscle and bone pathology and provided further evidence that associate pro-inflammatory host factors to RRV disease. This work has also demonstrated that bindarit should be considered as a candidate for treating RRV disease in humans.