Netsawang Janjuree, Panaampon Jutatip, Khunchai Sasiprapa, Kooptiwut Suwattanee, Nagila Amar, Puttikhunt Chunya, Yenchitsomanus Pa-Thai, Limjindaporn Thawornchai
Faculty of Medical Technology, Rangsit University, Phathum Thani, Thailand.
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.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1485-91. doi: 10.1016/j.bbrc.2014.07.016. Epub 2014 Jul 11.
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.
登革病毒（DENV）是黄病毒科的一种正链RNA病毒，有4种不同的血清型。DENV感染的临床表现包括登革热、登革出血热和登革休克综合征。在DENV感染后，在体外和体内均观察到肝细胞凋亡。然而，揭示病毒成分如何影响细胞凋亡的分子机制仍不清楚。在本研究中，通过RNA干扰和过表达研究对死亡结构域相关蛋白6（Daxx）在DENV介导的凋亡中的作用进行了表征，并确定了Daxx在DENV感染期间的抗凋亡功能。此外病毒成分，即DENV衣壳蛋白（DENV C），与Daxx相互作用，破坏Daxx与NF-κB之间的相互作用。释放的NF-κB激活了CD137的启动子，CD137是TNF家族的成员，先前已证明其在DENV感染期间可诱导凋亡。总之DENV C破坏Daxx与NF-κB的相互作用，在DENV感染期间诱导CD137介导的凋亡。
