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

J Hepatol. 2003 Mar;38(3):250-6. doi: 10.1016/s0168-8278(02)00418-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease Susceptibility
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / physiopathology*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Interferon-alpha / biosynthesis
  • Interleukin-6 / biosynthesis
  • Kupffer Cells / metabolism
  • Kupffer Cells / virology*
  • Microscopy, Electron
  • RNA, Viral / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Interferon-alpha
  • Interleukin-6
  • RNA, Viral
  • Tumor Necrosis Factor-alpha