Macrophage-induced muscle pathology results in morbidity and mortality forRoss River virus-infected mice

Ross River virus (RRV) is an Australian alphavirus that is often responsibl e for chronic epidemic polyarthritis and myalgia in humans. past studies ha ve shown severe disruption of striated muscle fibers to be prominent in RRV pathology in mice; in the present study, macrophages were directly implica ted as the primary mediators of muscle damage. General immunosuppressive th erapies had only minor effects on mortality and morbidity in RRV-infected m ice, with no inhibition of muscle damage. Treatment of mice with macrophage -toxic agents (e.g., silica) prior to RRV infection completely abrogated di sease symptoms without significantly affecting titers of virus in organs. F urther studies found that clinical signs of infection and muscle damage cor related with a massive influx of macrophages into hind leg muscle, whereas no such infiltrate or damage was observed for silica-treated mice. These ob servations are significant for the human disease context, as monocytic cell s have been detected in the synovial effusions of persons with epidemic pol yarthritis.