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Gene expression profiling by microarray analysis reveals an important role for caspase‐1 in dengue virus‐induced p53‐mediated apoptosis
Author(s) -
Nasirudeen A.M.A.,
Liu Ding Xiang
Publication year - 2009
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21486
Subject(s) - dengue virus , virology , gene expression profiling , biology , apoptosis , microarray analysis techniques , dengue fever , virus , microarray , gene , gene expression , dna microarray , caspase 3 , caspase 8 , genetics , programmed cell death
Abstract Recently, a dengue virus‐induced apoptosis p53‐ and mitochondria‐mediated were reported in human and animal cells. To understand further the underlying mechanisms, a p53‐deficient cell line, H1299, and a p53‐knockin cell line, H273, were infected with dengue type 1 virus and the cellular gene expression profiles at the mRNA level were analyzed by affymetrix array analysis. The results showed 183 genes with at least twofold increase at mRNA expression level in dengue virus‐infected cells. Among the 183 genes, 68 genes were up‐regulated in both H1299 and H273 cells and 78 genes were found to be up‐regulated in only H273 cells. Eleven selected genes, mainly involved in IFN‐pathway, cell cycle, signal transduction, and ubiquitin–proteasome pathways were confirmed using qualitative and quantitative PCR. Interestingly, an approximately 32‐fold increase in caspase‐1 expression was observed in the p53‐knockin cell line, H273. Gene silencing of caspase‐1 or inhibition of caspase‐1 activity led to reduction in dengue virus‐induced apoptosis with minimal effect on virus replication. J. Med. Virol. 81:1069–1081, 2009. © 2009 Wiley‐Liss, Inc.