Infection and direct injury in human hepatocyte explants and a hepatoblastoma cell line due to hepatiticomimetic (non-hepatitis) viruses

Hepatitis is caused by hepatitis viruses, but hepatitis or hepatocellular enzyme abnormalities is sometimes associated with infection by the hepatiticomimetic viruses. The direct and indirect effects of infection with hepatiticomimetic viruses were examined in two human hepatocyte systems. Poliovirus, adenovirus, and herpes simplex virus (HSV) induced cytopathology in Hep G2 cells. Measles virus caused no change in hepatocytes. Poliovirus infection did not affect cellular protein synthesis, and the peak of hepatocellular enzyme release coincided with the peak of virus release. The increase in adenovirus protein synthesis correlated with the decrease of transferrin synthesis, and enzyme release was not prominent. HSV induced viral protein synthesis with enhanced processing and inhibition of synthesis of α1-antitrypsin. The peak of enzyme release was later than the peak of virus release. In primary hepatocytes, poliovirus, adenovirus, and induced extensive cytopathology and enzyme release, and VZV caused cytopathology and significant but minute enzyme release. The ratio of lactate dehydrogenase to aspartate aminotransferase release was larger in poliovirus infection in both hepatocytes than in HSV or VZV infection. Although poliovirus and adenovirus are released by cytolysis and HSV and VZV are secreted by exocytosis of cytoplasmic vacuoles, enzyme release was independent of the type of virus release. Adenovirus showed strong cytotoxicity but did not modify the membrane nor cause enzyme release. Enzyme release was associated with modification of the surface membrane due to apoptosis with poliovirus and necrosis with HSV. Consequently hepatocellular injury by viral infection did not reflect the amount or pattern of hepatocellular enzyme release.