title: Dengue virus disrupts Daxx and NF-κB interaction to induce CD137-mediated apoptosis.
abstract: Dengue virus (DENV) is a positive-strand RNA virus of the Flavivirus family with 4 different serotypes. Clinical manifestations of DENV infection include dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Following DENV infection, apoptosis of hepatic cells is observed both in vitro and in vivo. However, the molecular mechanisms revealing how viral components affect cellular apoptosis remain unclear. In the present study, the role of death domain-associated protein 6 (Daxx) in DENV-mediated apoptosis was characterized by RNA interference and overexpression studies, and the anti-apoptotic function of Daxx during DENV infection was identified. Furthermore, the viral component, DENV capsid protein (DENV C), interacted with Daxx to disrupt interaction between Daxx and NF-κB. The liberated NF-κB activated the promoter of CD137, which is a member of the TNF family, and is previously shown to induce apoptosis during DENV infection. In summary, DENV C disrupts Daxx and NF-κB interaction to induce CD137-mediated apoptosis during DENV infection.
authors.affiliation: Faculty of Medical Technology, Rangsit University, Phathum Thani, Thailand.
authors.forename: Janjuree
authors.initials: J
authors.lastname: Netsawang
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Jutatip
authors.initials: J
authors.lastname: Panaampon
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sasiprapa
authors.initials: S
authors.lastname: Khunchai
authors.affiliation: Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Suwattanee
authors.initials: S
authors.lastname: Kooptiwut
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Amar
authors.initials: A
authors.lastname: Nagila
authors.affiliation: Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Thailand.
authors.forename: Chunya
authors.initials: C
authors.lastname: Puttikhunt
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: thawornchai.lim@mahidol.ac.th.
authors.forename: Thawornchai
authors.initials: T
authors.lastname: Limjindaporn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D056970:Co-Repressor Proteins; D017931:DNA Primers; D003716:Dengue Virus / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D018832:Molecular Chaperones; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D017931:DNA Primers; D018832:Molecular Chaperones; D016328:NF-kappa B; D009687:Nuclear Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: CD137; Daxx; Dengue virus; NF-kB