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Updated: Aug 9, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
p48 (ISGF-3gamma) is involved in interferon-alpha-induced suppression of hepatitis B virus enhancer-1 activity
K Nakao1, K Nakata, M Yamashita
1Health Research Center, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki 852-8501, Japan. kazuhiko@net.nagasaki-u.ac.jp
Abstract:
Interferon-alpha (IFN-alpha) suppresses hepatitis B virus (HBV) gene expression by reducing its enhancer-1 activity. IFN-alpha induces transcription factors, interferon-stimulated gene factor 3 (ISGF3), and interferon regulatory factor-1 (IRF-1), which activate interferon-inducible gene expression through binding to the interferon-stimulated regulatory element (ISRE) "AGTTTCNNTTTCNC" in the gene promoters. We found the ISRE-like sequence "AGGCTTTCACTTTCTC" in the HBV enhancer-1 region and elucidated the role of this sequence. Gel mobility shift assay showed binding of in vitro translated IRF-1 and in vitro translated p48 (ISGF3-gamma), which is a component of ISGF3 to this sequence. However, nuclear extracts binding to this sequence from human hepatoma cells (HuH-7) treated with IFN-alpha contained only the protein consisted of p48. In transfection experiments, IFN-alpha suppressed the HBV enhancer-1 activity, and overexpression of p48 enhanced this inhibitory effect. Both mutation and deletion of the ISRE-like sequence in the HBV enhancer-1 region reduced the suppressive effect of IFN-alpha. Our results suggest that the ISRE-like sequence in the HBV enhancer-1 can interact with the protein containing p48 and mediate the IFN-alpha-induced suppression of the enhancer activity.
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