Arthrogenic Alphaviruses and Inflammatory Myopathies

There is increasing evidence to suggest that viruses have aetiological roles in inflammatory myopathies. It has been reported that viruses, by means of direct infection of the skeletal muscle, can cause myalgias, polymyositis, and virus-associated rhabdomyolysis. It has also been found that some viruses can cause myositis through a secondary immune-mediated phenomenon. In addition, there are emerging reports of cases of idiopathic polymyositis suspected to be associated with infectious agents, predominantly viruses. Arthrogenic alphaviruses such as chikungunya virus (CHIKV), Ross River virus (RRV) and sindbis virus (SINV) are known to cause outbreaks of polyarthritis worldwide (Griffin, 2007). The clinical presentation of alphavirus infection includes fever, rash, arthralgia, and arthritis, however, one of the predominant features of alphaviral disease is myalgia with corresponding myositis. The recent outbreaks of CHIKV in several countries surrounding the Indian Ocean have seen millions of people affected, with case reports showing a high incidence of myalgia and skeletal muscle involvement. The ability of these viruses to cause long-term disease sequelae persisting for months or even years after the initial infection is of particular interest. Although difficult to substantiate indefinitely, there is significant reason to suspect that this long-term impact, combined with the virus‘s ability to cause acute muscle damage, could make arthrogenic viruses a potential cause of idiopathic inflammatory myopathies. The mechanisms by which alphaviruses cause musculoskeletal disease are now being unraveled with clear evidence to suggest that the viral-induced inflammatory response can lead to destruction of striated muscle fibres, providing a possible cause for the symptoms of myalgia. In recent years, the use of animal models of alphavirus-induced myositis has increased our understanding of the inflammatory myopathies caused by these viruses. Using these animal models it has been shown that in the acute phase of infection, skeletal muscle is the major site of viral replication, resulting in striated muscle fibre destruction (Lidbury et al., 2000; Morrison et al., 2006). In the sub-acute phase of infection, the virus triggers an extensive inflammatory immune response, resulting in the influx of inflammatory cells and production of soluble mediators, leading to extensive myositis. The use of animal models has been instrumental in elucidating the role of alphaviruses as triggers of inflammatory myopathies. This chapter will discuss the role of alphavirus infections as triggers of myositis, including how animal models are being used to dissect the pathobiology of disease and identify potential drug candidates to ameliorate disease.