Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8.
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)-1 beta , IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN- gamma , and tumor necrosis factor- alpha 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.
Hoshida
Yujin
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Kato
Naoya
N
Yoshida
Hideo
H
Wang
Yue
Y
Tanaka
Masamichi
M
Goto
Tadashi
T
Otsuka
Motoyuki
M
Taniguchi
Hiroyoshi
H
Moriyama
Masaru
M
Imazeki
Fumio
F
Yokosuka
Osamu
O
Kawabe
Takao
T
Shiratori
Yasushi
Y
Omata
Masao
M
D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D017930:Genes, Reporter; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics*
D018936:Hepatitis C Antigens; D016209:Interleukin-8; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D007372:Interferons