title: Role of CD137 signaling in dengue virus-mediated apoptosis.
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.
authors.affiliation: Medical Molecular Biology Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Amar
authors.initials: A
authors.lastname: Nagila
authors.forename: Janjuree
authors.initials: J
authors.lastname: Netsawang
authors.forename: Chatchawan
authors.initials: C
authors.lastname: Srisawat
authors.forename: Sansanee
authors.initials: S
authors.lastname: Noisakran
authors.forename: Atthapan
authors.initials: A
authors.lastname: Morchang
authors.forename: Umpa
authors.initials: U
authors.lastname: Yasamut
authors.forename: Chunya
authors.initials: C
authors.lastname: Puttikhunt
authors.forename: Watchara
authors.initials: W
authors.lastname: Kasinrerk
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.forename: Pa-thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: Thawornchai
authors.initials: T
authors.lastname: Limjindaporn
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003715:Dengue / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003716:Dengue Virus; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D015398:Signal Transduction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9