Pathogenesis of Ross River virus infection in mice. II. Muscle, heart, and brown fat lesions.

Abstract

In newborn mice infected subcutaneously with the NB5092 strain of Ross River virus there was early and extensive growth of virus in extraneural tissues, especially striate muscle, brown fat, and smooth muscle. Several days after peak titers had been attained in muscle, infected mice developed widespread muscle necrosis with paralysis of hind limbs, but recovery was complete by 35 days. In brown fat, lesions became calcified and were surrounded by giant cells; some lesions were not resolved by 60 days. The T48 strain of Ross River virus, unlike the NB5092 strain, regularly infected the heart and caused myocardial necrosis, and later, calcification. Both strains infected perichondrium, periosteum, and skin. Semliki Forest virus infected, with acute necrotic changes, the same extraneural tissues of newborn mice as did Ross River virus, but the infection was generally less extensive. Ross River virus (RRV) has been described as an etiologic agent of human epidemic polyarthritis in Australia [1]. RRV causes a paralytic disease in infant mice, and the studies on pathogenesis reported in the preceeding paper failed to implicate a neurologic mechanism for this paralysis. In the present paper the pathogenesis of lesions in striate, smooth, and cardiac muscle, as well as in connective tissue and brown fat, are described. The distribution of RRV in murine tissues has been briefly described [2], but in the present study the integrated use of immunofluorescence, light microscopic histology, electron microscopy, and viral assay of organs has allowed more comprehensive analysis of pathogenetic mechanisms.