Human hepatitis B virus enhancer 1 is responsive to human interleukin-6.

Abstract:

:Serum levels of interleukin-6 (IL-6) are elevated in acute and chronic hepatitis B patients. The effect of IL-6 and its transcription factor of NF-IL6 (a nuclear factor for IL-6) on hepatitis B virus (HBV) enhancer 1 (Enh1), which controls HBV X expression, were investigated in HepG2 cells. Twenty ng/ml of IL-6 increased 4-fold the enhancer activity of Enh1 according to the CAT assay. The IL-6 stimulation was abolished by introducing a mutation either in an AP-1-related site or a C-stretch sequence in the Enh1 sequence, demonstrating that the cis-elements are necessary for the IL-6 response. Co-transfection of NF-IL6 expression plasmid similarly increased the enhancer activity of Enh1 through both binding sites. Further, a specific complex formation of the Enh1 was detected using HepG2 nuclear lysates by electromobility shift assays, and the complex formation was increased in the lysates of cells treated with IL-6 and NF-IL6-transfection. In competition assays, one half of the complex formed was found to remain in the presence of 500-times excess competitor DNA fragment harboring NF-IL2 binding site, suggesting indirect binding of NF-IL6 to the Enh1 sequence. These results indicate that IL-6 increased the enhancer activity of HBV Enh1 through signal transduction pathways, indirectly involving NF-IL6, and may control HBV X expression and viral replication in HBV infected liver.

journal_name

J Med Virol

authors

Ohno H,Kaneko S,Kobayashi K,Murakami S

doi

10.1002/(sici)1096-9071(199708)52:4<413::aid-jmv12

subject

Has Abstract

pub_date

1997-08-01 00:00:00

pages

413-8

issue

4

eissn

0146-6615

issn

1096-9071

pii

10.1002/(SICI)1096-9071(199708)52:4<413::AID-JMV12

journal_volume

52

pub_type

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