Nonstructural proteins 4A and 4B of hepatitis C virus transactivate the interleukin 8 promoter.

Abstract:

:Interleukin 8 (IL-8) is induced in many cell types by various stimuli including virus infection. It was reported that nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) was involved in induction of IL-8 expression at both mRNA and protein levels in cultured human cells. In this study, we aimed to determine whether or not another HCV protein(s) transactivates the IL-8 gene expression, by means of an IL-8 promoter-driven luciferase reporter assay and measurement of endogenous IL-8 mRNA and secreted IL-8 protein levels. We observed that NS4B, and NS4A to a lesser extent, significantly transactivated the IL-8 promoter, which resulted in enhanced production of IL-8 protein. Also, the IL-8 expression was augmented in Huh-7 cells harboring an HCV subgenomic RNA replicon, compared with the control cells. Deletion mutational analysis of the IL-8 promoter revealed the possible involvement of the transcription factor AP-1 in both NS4A- and NS4B-mediated IL-8 gene activation. In addition, the IL-8 gene activation by NS4B, but not that by NS4A, was likely to involve NF-kappaB and/or NFIL-6. The degree of the transactivation by NS4B and NS4A varied with different human cell lines, with HeLa cells showing the strongest activation followed by Huh-7 cells, and with HepG2 cells exhibiting a marginal level of activation. Taken together, our present results suggest the possibility that NS4B and NS4A play an important role in inducing the IL-8 gene expression under certain cellular conditions, which might be one of the strategies to establish persistent HCV infection.

journal_name

Microbiol Immunol

authors

Kadoya H,Nagano-Fujii M,Deng L,Nakazono N,Hotta H

doi

10.1111/j.1348-0421.2005.tb03728.x

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

265-73

issue

3

eissn

0385-5600

issn

1348-0421

pii

JST.JSTAGE/mandi/49.265

journal_volume

49

pub_type

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