Murine adenovirus infection of SCID mice induces hepatic lesions that resemble human Reye syndrome

Abstract

Murine adenovirus type 1 (MAV-1) infection of CB-17 SCID mice (which are homozygous for the severe combined immunodeficiency mutation) induces hepatic histopathologic and ultrastructural features that are strikingly similar to human Reye syndrome. Gross pathologic examination of MAV-1-infected mice revealed only pale yellow liver tissue. Histopathologic studies of tissue from MAV-1-infected mice revealed diffuse hepatic injury manifested by microvesicular fatty degenerative changes of hepatocytes and electron microscopic evidence of focal mitochondrial swelling with disruption of cristae and depletion of glycogen. Serum aminotransferase activities increased markedly in the infected animals; however, plasma ammonia levels were not elevated at the times assayed. Although all mice infected with MAV-1 died, neutralizing anti-MAV-1 monoclonal antibodies provided a dose-dependent delay in the appearance of clinical disease and hepatic histopathologic findings. Other findings included rare viral inclusions with only minimal inflammation in spleen, adrenal, and liver of infected mice. Our findings indicate that MAV-1 infection of SCID mice may provide important insights into the pathogenesis of the hepatic lesions of Reye syndrome.