title: Dengue virus subgenomic RNA induces apoptosis through the Bcl-2-mediated PI3k/Akt signaling pathway.
abstract: 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.
authors: 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.
authors: Yi
authors: Y
authors: Liu
authors: Haibin
authors: H
authors: Liu
authors: Jing
authors: J
authors: Zou
authors: Bo
authors: B
authors: Zhang
authors: Zhiming
authors: Z
authors: Yuan
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D017124:Conserved Sequence; D003715:Dengue / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; Bcl-2; Cytopathicity; DENV-2; PI3k/Akt pathway; Subgenomic RNA