Role of CD137 signaling in dengue virus-mediated apoptosis

• Main Authors: Amar Nagila, Janjuree Netsawang, Chatchawan Srisawat, Sansanee Noisakran, Atthapan Morchang, Umpa Yasamut, Chunya Puttikhunt, Watchara Kasinrerk, Prida Malasit, Pa thai Yenchitsomanus, Thawornchai Limjindaporn
• Format: Journal
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79960050971&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/49703
• Institution: Chiang Mai University

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. © 2011 Elsevier Inc.