Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8

Yujin Hoshida, Naoya Kato, Hideo Yoshida, Yue Wang, Masamichi Tanaka, Tadashi Goto, Motoyuki Otsuka, Hiroyoshi Taniguchi, Maseru Moriyama, Fumio Imazeki, Osamu Yokosuka, Takao Kawabe, Yasushi Shiratori, Masao Omata

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background. We evaluated the association between variations in hepatitis C virus (HCV) core protein and hepatitis severity in patients with chronic HCV infection who achieved remission without viral eradication and had a biochemical response to interferon (IFN) therapy, to evaluate the effect of HCV core sequence in the absence of the influence of host factors. Methods. Using serum from 10 patients with a biochemical response and 10 patients with no response, we measured serum levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-γ, and tumor necrosis factor-α before and after IFN therapy. Expression vectors with the core region were transfected into Huh7 cells, and cytokine induction was evaluated by reporter assay. Results. In biochemical responders, only IL-8 levels decreased after IFN therapy (P = .04). Changes in the C-terminal hydrophobic region were observed more frequently in biochemical responders. Activation of the IL-8 promoter by HCV core protein was significantly decreased in biochemical responders after IFN therapy (P = .04). When 69 C-terminal amino acids from before IFN therapy were replaced with those from after IFN therapy in 3 biochemical responders, their ability to transactivate IL-8 decreased. Conclusions. Differences in amino acids in the HCV core protein correlates with hepatitis activity through the modulation of IL-8 induction in HCV-infected patients.

Original languageEnglish (US)
Pages (from-to)266-275
Number of pages10
JournalJournal of Infectious Diseases
Volume192
Issue number2
DOIs
StatePublished - Jul 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Hoshida, Y., Kato, N., Yoshida, H., Wang, Y., Tanaka, M., Goto, T., Otsuka, M., Taniguchi, H., Moriyama, M., Imazeki, F., Yokosuka, O., Kawabe, T., Shiratori, Y., & Omata, M. (2005). Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8. Journal of Infectious Diseases, 192(2), 266-275. https://doi.org/10.1086/430924