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Mol. Cells 2009; 28(1): 49-55

Published online July 31, 2009

https://doi.org/10.1007/s10059-009-0100-5

© The Korean Society for Molecular and Cellular Biology

Hepatitis Delta Virus Large Antigen Sensitizes to TNF-α-Induced NF-κB Signaling

Chul-Yong Park, Sang-Heun Oh, Sang Min Kang, Yun-Sook Lim, and Soon B. Hwang

Received: May 6, 2009; Revised: May 21, 2009; Accepted: May 22, 2009

Abstract

Hepatitis delta virus (HDV) infection causes fulminant hepatitis and liver cirrhosis. To elucidate the molecular mechanism of HDV pathogenesis, we examined the effects of HDV viral proteins, the small hepatitis delta antigen (SHDAg) and the large hepatitis delta antigen (LHDAg), on NF-κB signaling pathway. In this study, we demonstrated that TNF-α-induced NF-κB transcriptional activation was increased by LHDAg but not by SHDAg in both HEK293 and Huh7 cells. Furthermore, LHDAg promoted TRAF2-induced NF-κB activation. Using coimmunoprecipitation assays, we demonstrated that both SHDAg and LHDAg interacted with TRAF2 protein. We showed that isoprenylation of LHDAg was not required for the increase of NF-κB activity. We further showed that only LHDAg but not SHDAg increased the TNF-α-mediated nuclear translocation of p65. This was accomplished by activation of IκB-α degradation by LHDAg. Finally, we demonstrated that LHDAg augmented the COX-2 expression level in Huh7 cells. These data suggest that LHDAg modulates NF-κB signaling pathway and may contribute to HDV pathogenesis.

Keywords hepatitis delta virus, LHDAg, NF-κB, SHDAg, signal transduction

Article

Research Article

Mol. Cells 2009; 28(1): 49-55

Published online July 31, 2009 https://doi.org/10.1007/s10059-009-0100-5

Copyright © The Korean Society for Molecular and Cellular Biology.

Hepatitis Delta Virus Large Antigen Sensitizes to TNF-α-Induced NF-κB Signaling

Chul-Yong Park, Sang-Heun Oh, Sang Min Kang, Yun-Sook Lim, and Soon B. Hwang

Received: May 6, 2009; Revised: May 21, 2009; Accepted: May 22, 2009

Abstract

Hepatitis delta virus (HDV) infection causes fulminant hepatitis and liver cirrhosis. To elucidate the molecular mechanism of HDV pathogenesis, we examined the effects of HDV viral proteins, the small hepatitis delta antigen (SHDAg) and the large hepatitis delta antigen (LHDAg), on NF-κB signaling pathway. In this study, we demonstrated that TNF-α-induced NF-κB transcriptional activation was increased by LHDAg but not by SHDAg in both HEK293 and Huh7 cells. Furthermore, LHDAg promoted TRAF2-induced NF-κB activation. Using coimmunoprecipitation assays, we demonstrated that both SHDAg and LHDAg interacted with TRAF2 protein. We showed that isoprenylation of LHDAg was not required for the increase of NF-κB activity. We further showed that only LHDAg but not SHDAg increased the TNF-α-mediated nuclear translocation of p65. This was accomplished by activation of IκB-α degradation by LHDAg. Finally, we demonstrated that LHDAg augmented the COX-2 expression level in Huh7 cells. These data suggest that LHDAg modulates NF-κB signaling pathway and may contribute to HDV pathogenesis.

Keywords: hepatitis delta virus, LHDAg, NF-κ,B, SHDAg, signal transduction

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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