Yocupicio-Monroy Martha, Padmanabhan R, Medina Fernando, del Angel Rosa M
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, México City 03100, México.
Virology. 2007 Jan 5;357(1):29-40. doi: 10.1016/j.virol.2006.07.042. Epub 2006 Sep 7.
The untranslated regions (UTRs) of the positive and negative strand RNAs of several viruses are major binding sites for cellular and viral proteins. Human La autoantigen is one of the cellular proteins that interacts with various positive strand RNA viral genomes including that of dengue virus (DEN) within the 5'- and 3'-UTRs of positive (+) and the 3'-UTR of negative strand (-) RNA, and with the nonstructural proteins NS3 and NS5, that form DEN replicase complex. Since DEN replicates in human and mosquito cells, some functional interactions have to be conserved in both hosts. In the present report, we demonstrate that mosquito La protein interacts with the 3'-UTRs of (+) and (-) polarity viral RNAs. The localization of La protein, examined by confocal microscopy, indicates that La protein is redistributed in DEN-infected cells. Furthermore, the presence of La protein in an in vitro replication system inhibited RNA synthesis in a dose-dependent manner, suggesting that La protein plays an important role in dengue virus replicative cycle.
几种病毒的正链和负链RNA的非翻译区(UTRs)是细胞和病毒蛋白的主要结合位点。人La自身抗原是一种细胞蛋白,它与多种正链RNA病毒基因组相互作用,包括登革病毒(DEN)正链(+)的5'-和3'-UTR以及负链(-)RNA的3'-UTR,还与形成DEN复制酶复合物的非结构蛋白NS3和NS5相互作用。由于DEN在人类和蚊子细胞中复制,一些功能相互作用在这两种宿主中都必须保守。在本报告中,我们证明蚊子La蛋白与(+)和(-)极性病毒RNA的3'-UTR相互作用。通过共聚焦显微镜检查La蛋白的定位,表明La蛋白在DEN感染的细胞中重新分布。此外,体外复制系统中La蛋白的存在以剂量依赖的方式抑制RNA合成,这表明La蛋白在登革病毒复制周期中起重要作用。