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Nonstructural Proteins 4A and 4B of Hepatitis C Virus Transactivate the Interleukin 8 Promoter
Author(s) -
Kadoya Hiroyasu,
NaganoFujii Motoko,
Deng Lin,
Nakazono Naoki,
Hotta Hak
Publication year - 2005
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2005.tb03728.x
Subject(s) - transactivation , biology , ns5a , microbiology and biotechnology , hepatitis c virus , gene expression , reporter gene , promoter , subgenomic mrna , cell culture , gene , virus , virology , rna , hepacivirus , biochemistry , genetics
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‐κB 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.