Induction of p53-dependent and mitochondria-mediated cell death pathway by dengue virus infection of human and animal cells.
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.
Nasirudeen
A M A
AM
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos 138673, Singapore.
Wang
Li
L
Liu
Ding Xiang
DX
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
D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein