Infection of cardiomyocytes and induction of left ventricle dysfunction by neurovirulent polytropic murine retrovirus.

Viral infections of the heart are a causative factor of myocarditis as well as of sudden, unexpected deaths of children, yet the mechanisms of pathogenesis remain unclear, in part due to the relatively few animal models of virus-induced myocarditis. In the current study, we examined the ability of polytropic murine retroviruses to infect the heart and induce cardiac dysfunction. In situ hybridization and immunohistochemistry analysis detected virus-infected cardiomyocytes and macrophages in the heart. A significant decrease in left ventricle function, as measured by fractional shortening, was detected in mice infected with the neurovirulent retrovirus Fr98 but not in mice infected with the nonneurovirulent retrovirus Fr54. Virus infection was not associated with consistent findings of fibrosis or substantial cellular infiltrate. Fr98-induced left ventricle dysfunction was associated with a higher virus load, increased mRNA expression of the macrophage marker F4/80, increased chemokine production, and a small number of apoptotic cells in the heart.

Ligand up-regulation does not correlate with a role for CCR1 in pathogenesis in a mouse model of non-lymphocyte-mediated neurological disease.

CCR1 ligands, including CCL3, CCL5, and CCL7, are up-regulated in a number of neurological disorders in humans and animal models. CCR1 is expressed by multiple cell types in the central nervous system (CNS), suggesting that receptor signaling by neuronal cell types may influence pathogenesis. In the current study, the authors used a mouse model of retrovirus infection to study the contribution of CCR1 to neuropathogenesis in the absence of lymphocyte recruitment to the CNS. In this model, infection of neonatal mice with the neurovirulent retrovirus Fr98 results in increased expression of proinflammatory chemokines in the CNS, activation of glial cells, and development of severe neurological disease. Surprisingly, no difference in neuropathogenesis was observed between CCR1-sufficient and CCR1-deficient mice following infection with the neuropathogenic virus Fr98. CCR1 was also not necessary for control of virus replication in the brain or virus-induced activation of astroglia. Additionally, CCR1 deficiency did not affect the up-regulation of its ligands, CCL3, CCL5, or CCL7. Thus, CCR1 did not appear to have a notable role in Fr98-induced pathogenesis, despite the correlation between ligand expression and disease development. This suggests that in the absence of inflammation, CCR1 may have a very limited role in neuropathogenesis.