Electron and immunoelectron microscopic study on liver tissues of marmosets infected with hepatitis A virus

Electron and immunoelectron microscopic studies were carried out on liver tissues from three marmosets, experimentally infected with hepatitis A virus and sacrificed during the acute phase of illness. Ultrastructurally, the liver cells demonstrated marked cisternal dilation of endoplasmic reticulum and vesicular transformation and contortion of endoplasmic reticulum profiles. Clusters of virus-like particles of 24 to 27 nm. in diameter, both "solid" and "empty" forms, were found in membrane-bound cytoplasmic vesicles. In one animal, the virus-like particles were significantly smaller, measuring 17 to 22 nm. in size, and almost all were solid forms embedded in an amorphous matrix. Clusters of virus-like particles were found in the bile canaliculi of liver cell cords and in lysosomal structures of monocytes or Kupffer cells in the hepatic sinusoids. The latter correlated with the immunofluorescent microscopic finding. Indirect immunoferritin staining was carried out on fresh and formalin-fixed liver tissues, using convalescent phase serum from patients recovered from hepatitis A virus infection as the primary antibody, and the ferritin-labeled rabbit anti-human IgG or ferritin-labeled staphylococcal protein A as the secondary antibody. Specific stainings were observed with the virus-like particles, indicating that the particles were probably antigenically related to hepatitis A virus. Our findings are in agreement with the immunofluorescent and immunoelectron microscopic studies reported by others and support the concept that hepatitis A virus is produced in the liver. The infection seems to produce cytopathic effect especially to the endoplasmic reticulum organelle of hepatocytes.