Differential expression of CX3CL1 in hepatitis B virus-replicating hepatoma cells can affect the migration activity of CX3CR1+ immune cells

Yasuteru Kondo, Osamu Kimura, Yasuhito Tanaka, Masashi Ninomiya, Tomoaki Iwata, Takayuki Kogure, Jun Inoue, Masaya Sugiyama, Tatsuki Morosawa, Yasuyuki Fujisaka, Tooru Shimosegawa

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5 Citations (Scopus)

Abstract

In addition to stellate cells and immune cells, inflamed hepatocytes and hepatoma cells express various kinds of chemokines that attract various kinds of immune cells. Previously, we reported that hepatitis B virus (HBV) replication can induce physiological stress. The aim of this study was to analyze the effect of chemokines produced by HBV-infected hepatocytes and hepatoma cells. A real-time PCR array targeting genes related to chemokines and enzyme-linked immunosorbent assay (ELISA) were carried out to detect the specific chemokines produced by Huh7 cells and HepG2 cells infected with various HBV genotypes. A migration assay, flow cytometry analysis, and immunohistochemistry were carried out to analyze the candidate immune cells that can affect the immunopathogenesis of HBV infection. The expressions of CX3CL1 mRNA and protein were significantly different among HBV genotypes A, B, and C and control cells (mock) (P<0.05). CD56+ NK cells and CD8+ T cells migrated to the hepatoma cells with HBV replication. Moreover, the migration activity of both immune cells was partially cancelled after the treatment of CX3CL1 neutralizing antibody. The expression level of NKG2D on CX3CR1+ NK cells in HCC with HBV infection was significantly lower than that in hepatocellular carcinoma (HCC) with HCV infection and chronic hepatitis B and C patients (P<0.05). On the other hand, the frequency of PD-1high CX3CR1+ CD8+ T cells in HCC with HBV infection was significantly higher than that in HCC with HCV infection and chronic hepatitis B and C (P<0.05). The expression of CX3CL1 in HBV-replicating hepatocytes and hepatoma cells could contribute to the immunopathogenesis of HBV infection.

Original languageEnglish
Pages (from-to)7016-7027
Number of pages12
JournalJournal of virology
Volume89
Issue number14
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Kondo, Y., Kimura, O., Tanaka, Y., Ninomiya, M., Iwata, T., Kogure, T., Inoue, J., Sugiyama, M., Morosawa, T., Fujisaka, Y., & Shimosegawa, T. (2015). Differential expression of CX3CL1 in hepatitis B virus-replicating hepatoma cells can affect the migration activity of CX3CR1+ immune cells. Journal of virology, 89(14), 7016-7027. https://doi.org/10.1128/JVI.00716-15