A study of susceptibility of primary human Kupffer cells to hepatitis C virus

Background/Aims: Histological examination of a liver-biopsy from a patient with chronic hepatitis C shows activated Kupffer cells. In vitro infection of human Kupffer cells (KC) was performed to study their interaction with hepatitis C virus (HCV). Methods: KC, isolated by collagenase perfusion and centrifugal elutriation, were infected with various HCV positive sera. The presence of the viral genome was followed, at different times, quantitatively by a branched-DNA assay and qualitatively by reverse transcriptase-nested polymerase chain reaction. A strand-specific assay performed with the thermostable enzyme rTth was used to detect the synthesis of a negative replicative intermediate. Cytopathic effect was examined by electron microscopy. Production of cytokines and inducible nitric oxide synthase was evaluated in the supernatants. Results: Quantification of HCV-RNA showed that the level of viral RNA associated with KC after adsorption decreased rapidly. Genomic viral RNA disappeared within 5 days of infection. Negative-strand RNA was never detected in any of these experiments. No cytopathic effects could be detected at any time. KC did not produce inflammatory nor antiviral cytokines. Conclusions: Our results strongly suggest that primary cultures of KC are not permissive for HCV in vitro. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.