Kurosu Takeshi, Chaichana Panjaporn, Yamate Masanobu, Anantapreecha Surapee, Ikuta Kazuyoshi
Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Tiwanon Rd, Muang, Nonthaburi 11000, Thailand.
Biochem Biophys Res Commun. 2007 Nov 3;362(4):1051-6. doi: 10.1016/j.bbrc.2007.08.137. Epub 2007 Aug 30.
Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). It has been suggested that patients with an elevated level of the free soluble form of dengue virus (DV) nonstructural protein 1 (sNS1) are at risk of developing DHF. To understand the role of sNS1 in blood, we searched for the host molecule with which NS1 interacts in human plasma by affinity purification using a GST-fused NS1. Complement inhibitory factor clusterin (Clu), which naturally inhibits the formation of terminal complement complex (TCC), was identified by mass spectrometry. A recombinant sNS1 produced from 293T cells and sNS1 from DV-infected Vero cells interacted with human Clu. Since an activated complement system reportedly causes vascular leakage, the interaction between sNS1 and Clu may contribute to the progression of DHF.
血管渗漏和休克是登革出血热（DHF）和登革休克综合征（DSS）患者死亡的主要原因。有研究表明，登革病毒（DV）非结构蛋白1（NS1）的游离可溶性形式（sNS1）水平升高的患者有发生DHF的风险。为了解sNS1在血液中的作用，我们通过使用谷胱甘肽S-转移酶（GST）融合的NS1进行亲和纯化，在人血浆中寻找与NS1相互作用的宿主分子。通过质谱鉴定出天然抑制末端补体复合物（TCC）形成的补体抑制因子簇集素（Clu）。从293T细胞产生的重组sNS1和来自DV感染的Vero细胞的sNS1与人Clu相互作用。由于据报道活化的补体系统会导致血管渗漏，因此sNS1与Clu之间的相互作用可能有助于DHF的进展。
