title: Induction of p53-dependent and mitochondria-mediated cell death pathway by dengue virus infection of human and animal cells.
abstract: Previous studies have suggested that cells undergo apoptosis in response to dengue virus infection. However, the potential significance of dengue virus-induced apoptosis and the pathways are still not clearly defined. In this study, comparative analysis of dengue virus-induced apoptosis in BHK, H1299, HUH-7 and Vero cell lines was carried out. We show here that infection of BHK, HUH-7 and Vero cell lines with dengue type 1 virus (DEN1V) induces cell death typical of apoptosis. Virus-induced cell death was assayed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, detection of oligonucleosomal DNA fragmentation, DNA content analysis and assay for the externalization of phosphatidylserine residues. Detailed study of dengue virus infection in HUH-7 cells showed activation of cell death via the mitochondrial pathway causing lowering of mitochondrial transmembrane potential (DeltaPsim) in HUH-7 cells. Interestingly, in the p53-deficient cell line, H1299, apoptosis was largely undetectable compared with the other cell lines used; suggesting that a p53- and mitochondria-mediated cell death pathway may play an important role in dengue virus-induced apoptosis.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos 138673, Singapore.
authors.forename: A M A
authors.initials: AM
authors.lastname: Nasirudeen
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Ding Xiang
authors.initials: DX
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D014709:Vero Cells; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein