La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Antiviral Res. 2013 Apr;98(1):35-43. doi: 10.1016/j.antiviral.2013.01.004. Epub 2013 Jan 31.
The aim of the present study was to evaluate the ability of the iminosugar drug UV-4 to provide in vivo protection from lethal dengue virus (DENV) challenge. This study utilized a well-described model of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS)-like lethal disease in AG129 mice lacking the type I and II interferon receptors. Herein, we present UV-4 as a potent iminosugar for controlling DENV infection and disease in this mouse model. Specifically, administration of UV-4 reduced mortality, as well as viremia and viral RNA in key tissues, and cytokine storm. In addition, UV-4 treatment can be delayed, and it does not alter the anti-DENV antibody response. These results have set the foundation for development of UV-4 as a DENV-specific antiviral in phase I human clinical trials.
本研究旨在评估氨基糖药物 UV-4 提供体内保护以避免致命登革热病毒（DENV）感染的能力。该研究利用缺乏 I 型和 II 型干扰素受体的 AG129 小鼠中描述良好的登革出血热/登革休克综合征（DHF/DSS）样致死性疾病模型。在此，我们提出 UV-4 是控制该小鼠模型中 DENV 感染和疾病的有效氨基糖。具体而言，UV-4 给药可降低死亡率以及关键组织中的病毒血症和病毒 RNA，并减少细胞因子风暴。此外，UV-4 治疗可以延迟进行，且不会改变抗 DENV 抗体反应。这些结果为 UV-4 作为 I 期人体临床试验中的 DENV 特异性抗病毒药物的开发奠定了基础。
