Lai Chih-Yun, Hu Hsien-Ping, King Chwan-Chuen, Wang Wei-Kung
Institute of Microbiology, College of Medicine, National Taiwan University, No.1 Sec.1 Jen-Ai Rd, Taipei, Taiwan.
J Biomed Sci. 2008 Jan;15(1):15-27. doi: 10.1007/s11373-007-9204-0. Epub 2007 Aug 31.
While virus-like particles (VLPs) containing subgenomic replicons, which can transduce replicons into target cells efficiently for studying viral replication and vectors of gene therapy and vaccine, have been established for several flaviviruses, none has been reported for the four serotypes of dengue virus, the causal agent of the most important arboviral diseases in this century. In this study, we successfully established a cell line stably expressing the precursor membrane/envelope (PrM/E) proteins of dengue virus type 2 (DENV2), which can package a DENV2 replicon with deletion of PrM/E genes and produce single-round infectious VLPs. Moreover, it can package a similar replicon of different serotype, dengue virus type 4, and produce infectious chimeric VLPs. To our knowledge, this study reports for the first time replicon-containing VLPs of dengue virus. Moreover, this convenient system has potential as a valuable tool to study encapsidation of dengue virus and to develop novel chimeric VLPs containing dengue virus replicon as vaccine in the future.
虽然含有亚基因组复制子的病毒样颗粒(VLPs)已被用于多种黄病毒,可有效地将复制子转导到靶细胞中以研究病毒复制以及作为基因治疗和疫苗的载体,但对于本世纪最重要的虫媒病毒病的病原体——登革病毒的四种血清型,尚未见相关报道。在本研究中,我们成功建立了一个稳定表达登革病毒2型(DENV2)前体膜/包膜(PrM/E)蛋白的细胞系,该细胞系能够包装缺失PrM/E基因的DENV2复制子并产生单轮感染性VLPs。此外,它还能包装不同血清型的类似复制子——登革病毒4型,并产生感染性嵌合VLPs。据我们所知,本研究首次报道了含有登革病毒复制子的VLPs。此外,这个便捷的系统有潜力成为研究登革病毒包装以及未来开发含有登革病毒复制子的新型嵌合VLPs作为疫苗的宝贵工具。