Coxsackievirus B 1-induced polymyositis. Lack of disease expression in nu/nu mice.

Abstract

Chronic inflammatory myositis similar to human polymyositis occurs in mice after infection with a strain of Coxsackievirus B 1 (CVB 1). To investigate the role of T cells in the pathogenesis of this disorder, we compared disease expression in T cell-deficient athymic nude (nu/nu) mice and heterozygotes (nu/+) with normal T cell function. Acute infectious myositis occurred in nu/ nu and nu/+ mice. Chronic (> 21 d postinfection) weakness and myositis, however, developed only in nu/+. Resistance to disease in nu/nu mice was not explained by insusceptibility to infection; the amount of virus lethal for 50% of mice and virus replication were comparable in both groups. Additionally, anti-CVB 1 antibody production was similar in both groups. Reconstitution of infected nu/nu mice with spleen cells from normal mice resulted in disease. These results demonstrate that chronic weakness after infection with this virus is not simply a sequela of acute myonecrosis and suggest that T cells play a pivotal role in the pathogenesis of chronic myositis.

Predominant right leg dysfunction without asymmetric muscle inflammation in CD1 Swiss mice with coxsackievirus B1-induced myositis

“…In contrast to other murine models for polym yositis (23,26), the m otor abnormalities in CB1 myositis have been reported to be asymmetric, suggesting the predominant involvem ent of one limb (24,27,32,35,36). C uri ously, the right leg seem ed m ore affected than the left one, both on observation and on qualitative m icroscopy (26,27,32,35). At present, however, no quantified observational data have been reported on predominant right leg dysfunction in C B 1 (24,26,27,32,35,36); no plausible explanation has been put forward for the right leg bias.…”

“…C uri ously, the right leg seem ed m ore affected than the left one, both on observation and on qualitative m icroscopy (26,27,32,35). At present, however, no quantified observational data have been reported on predominant right leg dysfunction in C B 1 (24,26,27,32,35,36); no plausible explanation has been put forward for the right leg bias. To answer these ques tions, we quantified m otor asym m etries in mice with CB1 myosi tis on repeated observation and studied mononuclear cell infiltra tion and muscle fiber necrosis in right-and left-sided hamstring muscles on quantitative microscopy.…”

“…Severely affected animals develop a flexion deform ity (27,32). In contrast to other murine models for polym yositis (23,26), the m otor abnormalities in CB1 myositis have been reported to be asymmetric, suggesting the predominant involvem ent of one limb (24,27,32,35,36). C uri ously, the right leg seem ed m ore affected than the left one, both on observation and on qualitative m icroscopy (26,27,32,35).…”

“…After 2 weeks the inflammation devel ops into a chronic phase, CBI-induced myositis (CB1 myositis), when virus can no longer be cultured from muscle tissue (27,32). CB1 myositis is thought to have an autoimmune origin and only occurs in the presence of T lymphocytes (35,36). For its clinical, electromyographic, and histological resemblance to human polymyositis (K), CB1 myositis is considered an experimental model for polymyositis (26,32), Like the preceding acute viral myositis, CB1 myositis principally involves the proximal hind leg muscles, and weakness show s itself as decreased mobility, abnor mal posture, and a waddling gait (24,26,27,32).…”

Non-Polio Enteroviruses, the Neglected and Emerging Human Pathogens:Are we Waiting for the Sizzling Enterovirus Volcano to Erupt?

“…EVs are also known to cause persistent infections in humans, lasting for several months (Martin 2004;Martin 2006;Li et al, 2013). This wide variation in the degree of disease symptoms likely reflects the significant genetic variation not only among different enterovius serotypes, but within strains belonging to 458 C Durga Rao the same serotype (Borzakian et al, 1993;Duncan et al, 1998;Ramsingh and Collins 1995;Coleman et al, 2008;Yetterberg et al, 1987;Song et al, 2012;Rao et al, 2012;Rao et al, 2013;Rao et al, 2014).…”