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

15 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Interleukin-8
Interferons
Transcriptional Activation
Hepatitis
Hepacivirus
Therapeutics
Amino Acids
Chronic Hepatitis C
Virus Diseases
Interleukin-12
Hepatitis C virus nucleocapsid protein
Serum
Interleukin-1
Interleukin-4
Interleukin-10
Interleukin-2
Interleukin-6
Tumor Necrosis Factor-alpha
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8. / Hoshida, Yujin; Kato, Naoya; Yoshida, Hideo; Wang, Yue; Tanaka, Masamichi; Goto, Tadashi; Otsuka, Motoyuki; Taniguchi, Hiroyoshi; Moriyama, Maseru; Imazeki, Fumio; Yokosuka, Osamu; Kawabe, Takao; Shiratori, Yasushi; Omata, Masao.

In: Journal of Infectious Diseases, Vol. 192, No. 2, 15.07.2005, p. 266-275.

Research output: Contribution to journalArticle

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, vol. 192, no. 2, pp. 266-275. https://doi.org/10.1086/430924
Hoshida, Yujin ; Kato, Naoya ; Yoshida, Hideo ; Wang, Yue ; Tanaka, Masamichi ; Goto, Tadashi ; Otsuka, Motoyuki ; Taniguchi, Hiroyoshi ; Moriyama, Maseru ; Imazeki, Fumio ; Yokosuka, Osamu ; Kawabe, Takao ; Shiratori, Yasushi ; Omata, Masao. / Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8. In: Journal of Infectious Diseases. 2005 ; Vol. 192, No. 2. pp. 266-275.
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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.",
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AU - Yoshida, Hideo

AU - Wang, Yue

AU - Tanaka, Masamichi

AU - Goto, Tadashi

AU - Otsuka, Motoyuki

AU - Taniguchi, Hiroyoshi

AU - Moriyama, Maseru

AU - Imazeki, Fumio

AU - Yokosuka, Osamu

AU - Kawabe, Takao

AU - Shiratori, Yasushi

AU - Omata, Masao

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