Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of the Chinese Academy of Sciences, Beijing 100039, China.
Virology. 2014 Jan 5;448:15-25. doi: 10.1016/j.virol.2013.09.016. Epub 2013 Oct 16.
We report a RNA species of 429 nucleotides derived from the 3' untranslated region of the viral genome in Dengue 2 virus (DENV-2) infected cells. The 3' terminal of viral RNA contained specific conserved structures that are important for the production of subgenomic RNA. Transient replicon assays suggested that loss of this small RNA has little effect on viral replication, and genetic analysis using recombinant viruses demonstrated that the existence of this subgenomic RNA is not essential for the life cycle of the DENV-2. Results from cytotoxicity and apoptosis assay revealed that the generation of subgenomic RNA is significant for DENV-2 viral cytopathicity and virus-induced apoptosis; and the deficiency could be partially restored by providing subgenomic RNA in trans from transfection. In addition, we found that subgenomic RNA modulates the phosphatidylinositol 3-kinase (PI3k)/Akt signaling pathway through a Bcl-2-related mechanism, resulting in apoptotic cell death.
我们报道了一种来自登革热 2 型病毒（DENV-2）感染细胞中病毒基因组 3'非翻译区的 429 个核苷酸的 RNA 种类。病毒 RNA 的 3'末端包含特定的保守结构，这些结构对亚基因组 RNA 的产生很重要。瞬时复制子试验表明，这种小 RNA 的缺失对病毒复制的影响很小，而使用重组病毒的遗传分析表明，这种亚基因组 RNA 的存在对于 DENV-2 的生命周期并不是必需的。细胞毒性和细胞凋亡试验的结果表明，亚基因组 RNA 的产生对 DENV-2 病毒的细胞病变和病毒诱导的细胞凋亡至关重要；而通过转染提供亚基因组 RNA 可以部分恢复缺陷。此外，我们发现亚基因组 RNA 通过一种 Bcl-2 相关的机制调节磷脂酰肌醇 3-激酶（PI3k）/Akt 信号通路，导致细胞凋亡死亡。
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