Role of CD137 signaling in dengue virus-mediated apoptosis

• Published in: Biochemical and biophysical research communications Vol. 410; no. 3; pp. 428 - 433
• Main Authors: Nagila, Amar, Netsawang, Janjuree, Srisawat, Chatchawan, Noisakran, Sansanee, Morchang, Atthapan, Yasamut, Umpa, Puttikhunt, Chunya, Kasinrerk, Watchara, Malasit, Prida, Yenchitsomanus, Pa-thai, Limjindaporn, Thawornchai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08-07-2011
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; ANTIBODIES; APOPTOSIS; CD137 signaling; Cell Line, Tumor; DEATH; Dengue - genetics; Dengue - metabolism; Dengue - pathology; Dengue Virus; Dengue virus capsid protein; GENES; Humans; INJURIES; LIVER; Liver - metabolism; Liver - pathology; Liver - virology; MESSENGER-RNA; MUTATIONS; POLYMERASE CHAIN REACTION; RADIOPROTECTIVE SUBSTANCES; RECEPTORS; Signal Transduction; Tumor Necrosis Factor Receptor Superfamily, Member 9 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 9 - metabolism; VIRUSES; Dengue virus capsid protein; Dengue virus; CD137 signaling; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.05.151

► For the first time the role of CD137 in dengue virus (DENV) infection. ► Induction of DENV-mediated apoptosis by CD137 signaling. ► Sensitization to CD137-mediated apoptosis by dengue virus capsid protein (DENV C). ► Nuclear localization of DENV C is required for CD137-mediated apoptosis.
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.