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Role of CD137 signaling in dengue virus-mediated apoptosis.

Authors :: Nagila A
Netsawang J
Srisawat C
Noisakran S
Morchang A
Yasamut U
Puttikhunt C
Kasinrerk W
Malasit P
Yenchitsomanus PT
Limjindaporn T
Source :: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2011 Jul 08; Vol. 410 (3), pp. 428-33. Date of Electronic Publication: 2011 Jun 06.
Publication Year :: 2011
Abstract: Hepatic dysfunction is a well recognized feature of dengue virus (DENV) infection. However, molecular mechanisms of hepatic injury are still poorly understood. A complex interaction between DENV and the host immune response contributes to DENV-mediated tissue injury. DENV capsid protein (DENV C) physically interacts with the human death domain-associated protein Daxx. A double substitution mutation in DENV C (R85A/K86A) abrogates Daxx interaction, nuclear localization and apoptosis. Therefore we compared the expression of cell death genes between HepG2 cells expressing DENV C and DENV C (R85A/K86A) using a real-time PCR array. Expression of CD137, which is a member of the tumor necrosis factor receptor family, increased significantly in HepG2 cells expressing DENV C compared to HepG2 cells expressing DENV C (R85A/K86A). In addition, CD137-mediated apoptotic activity in HepG2 cells expressing DENV C was significantly increased by anti-CD137 antibody compared to that of HepG2 cells expressing DENV C (R85A/K86A). In DENV-infected HepG2 cells, CD137 mRNA and CD137 positive cells significantly increased and CD137-mediated apoptotic activity was increased by anti-CD137 antibody. This work is the first to demonstrate the contribution of CD137 signaling to DENV-mediated apoptosis.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)