Synergistic activation of the serum response element-dependent pathway by hepatitis B virus x protein and large-isoform hepatitis delta antigen.
Hepatitis delta virus (HDV) is a naturally occurring satellite of hepatitis B virus (HBV). There are few studies of the effects of the combination of HBV and HDV proteins (HDV antigens [HDAgs]) on intracellular signaling pathways. To understand the influence of HBV and HDV coinfection on hepatocytes, we investigated the effect of HBV proteins and HDAgs on the serum response element (SRE)-dependent pathway. Reporter assays revealed that only HBV X protein (HBx), alone or with the large isoform of HDAg (LHDAg), synergistically activated the SRE-dependent pathway. The effect of HBx and LHDAg on Elk1 or serum response factor (SRF) was examined, because both proteins bind to the SRE. HBx activated the transcriptional ability of Elk1, whereas LHDAg activated the transcriptional ability of SRF. Thus, HBx and LHDAg synergistically activated the SRE-dependent pathway. These results may help us understand clinical phenomena in patients coinfected with HBV and HDV.
Goto
Tadashi
T
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Kato
Naoya
N
Yoshida
Hideo
H
Otsuka
Motoyuki
M
Moriyama
Masaru
M
Shiratori
Yasushi
Y
Koike
Katsuro
K
Matsumura
Masayuki
M
Omata
Masao
M
D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D035923:Hepatitis delta Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D027602:Serum Response Element / Q000235:genetics*; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D035923:Hepatitis delta Antigens; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D050807:ets-Domain Protein Elk-1; C057628:hepatitis B virus X protein