Hepatitis C Virus Core Protein Inhibits Interleukin 12 and Nitric Oxide Production From Activated Macrophages

Virology. 2001 Jan 5;279(1):271-9. doi: 10.1006/viro.2000.0694.

Abstract

A characteristic feature of hepatitis C virus (HCV) infection is a high frequency of persistence and the progression to chronic liver diseases. Recent data suggest that prevalent T helper (Th) 2 immunity as well as weak HCV-specific T-cell response is associated with viral persistence. Here, we showed that the production of interleukin 12 (IL-12) and nitric oxide (NO) that is critical for the induction of Th1 and innate immunity, but not that of tumor necrosis factor alpha (TNF-alpha), was significantly suppressed in both HCV core-expressing macrophage cell lines and mouse peritoneal macrophages treated with recombinant core protein. In addition, IL-12 p40 promoter activity was repressed by the presence of HCV core in macrophages stimulated with lipopolysaccharride (LPS) following IFN-gamma treatment, indicating that IL-12 production may be downregulated at the transcriptional level. We also found that proliferation of T cells and IFN-gamma production in mixed lymphocyte reactions (MLR) with core-expressing cells were inhibited. Taken together, our results suggest that HCV core protein could play roles in suppressing the induction of Th1 immunity through inhibition of IL-12 and NO production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Hepacivirus / physiology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis*
  • Lymphocyte Culture Test, Mixed
  • Macrophage Activation*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / virology*
  • Macrophages, Peritoneal / virology
  • Mice
  • Mice, Transgenic
  • Monocytes
  • Nitric Oxide / biosynthesis*
  • Recombinant Proteins / pharmacology
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism
  • Viral Core Proteins / pharmacology
  • Viral Core Proteins / physiology*

Substances

  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma