HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Matsuda, T. Articles by Mori, N. Search for Related Content PubMed PubMed Citation Articles by Matsuda, T. Articles by Mori, N. Agricola Articles by Matsuda, T. Articles by Mori, N.

Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand

¹ Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 903-0215, Japan
² Division of Child Health and Welfare, Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 903-0215, Japan
³ Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
⁴ Department of Immunology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan

Correspondence
Naoki Mori
n-mori{at}med.u-ryukyu.ac.jp

Although hepatic injury is reported in cases with dengue haemorrhagic fever and dengue shock syndrome, its mechanism remains poorly understood. Several findings suggest that dengue virus (DEN) induces apoptosis of hepatocytes in vivo. In this work, DEN type 2 (DEN-2) strain NGC was shown to induce apoptosis in the hepatic cell line HepG2, and infection of HepG2 cells was found to induce Apo2 ligand (Apo2L, also known as tumour necrosis factor-related apoptosis-inducing ligand or TRAIL) expression. Furthermore, Apo2L/TRAIL induced apoptosis in HepG2 cells, which expressed the Apo2L/TRAIL receptor DR5/TRAIL-R2 on their surface. Analysis of the Apo2L/TRAIL promoter revealed that this gene was activated by DEN-2 infection, whose responsive element was overlapping NF-B- and Sp1-binding sites located at nt –75 to –65. The proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL) inhibited Apo2L/TRAIL mRNA expression, and LLnL and anti-Apo2L/TRAIL antibody inhibited DEN-2-induced apoptosis. It was proposed that DEN infection promotes apoptosis partly through the induction of Apo2L/TRAIL expression.

This article has been cited by other articles:

				T. Peng, J. Zhu, Y. Hwangbo, L. Corey, and R. E. Bumgarner Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts J. Virol., February 15, 2008; 82(4): 1934 - 1945. [Abstract] [Full Text] [PDF]

				R. V. Warke, K. J. Martin, K. Giaya, S. K. Shaw, A. L. Rothman, and I. Bosch TRAIL Is a Novel Antiviral Protein against Dengue Virus J. Virol., January 1, 2008; 82(1): 555 - 564. [Abstract] [Full Text] [PDF]