{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Justin Ooi"],"organism":["Homo sapiens"],"software":["Partek"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-16201"],"description":["Primary human monocytes were isolated and differentiated into moDCs. These moDCs were infected with WT Dengue virus 2 and its attenuated mutants (generated using infectious clone construction with site-directed mutagenesis) to better understand the gene expression changes induced by these different attenuated viruses."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - Total RNA was extracted using the RNeasy Mini Kit. The quality of the RNA samples was assessed by Bioanalyzer.","Sample Collection - Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood collected from a flavivirus-naïve healthy donor. Cells were incubated at 37°C for 2.5 hr to allow monocytes to adhere to the tissue culture flask surface. Monocytes were incubated overnight at 37°C before use in experiments","Labeling - Fragmented, labelled single-stranded cDNA were prepared from 200ng of total RNA using Affymetrix GeneChip Whole Transcript (WT) PLUS Reagent Kit, according to the manufacturer’s instructions. Each DNA fragment was end-labeled with biotin using terminal deoxynucleotidyl transferase before hybridization on the arrays.","Hybridization - Hybridization cocktails containing fragmented, end-labeled cDNA were prepared and applied to GeneChip Human Gene 2.0 ST arrays. Hybridization was performed at 60 rpm for 16h at 45°C using the FS450_0001 fluidics protocol.","Scaning - Scanning was done using the GeneChip® Scanner 3000 7G (Affymetrix Inc., Santa Clara, CA) and Affymetrix GeneChip Command Console Software (AGCC) to produce .CEL intensity files."],"figure_sub":["MIAME Score","Raw Data","Organization","Assays and Data","Processed Data","MAGE-TAB Files","Array Designs"],"data_protocol":["Data Transformation - Microarray .CEL files were imported into Partek Genomics Suite v7.21 (PGS) for gene assignment and intensity signal was quantile-normalized and log2 transformed."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"pubmed_abstract":["To successfully complete an infection lifecycle, viruses have to avoid activating host antiviral and transcriptional responses to avoid disrupting cellular processes and cause premature host cell death. How the host transcriptional response to dengue virus (DENV) infection and its impact on pathogenesis, however, remain unclear. Herein, we examined a pair of DENV-2, where the wild-type strain (16681) elicited few host transcriptional responses following infection, in contrast to its clinically tested attenuated derivative (PDK53 strain). Site-directed mutagenesis studies revealed a single D29V substitution on the pre-membrane (prM) protein, present not in 16681 but in PDK53, that altered transcriptional response to infection. Mechanistically, prM D29V substitution impaired interaction of prM protein with host high mobility group box 1 (HMGB1) protein; wild-type prM-HMGB1 interaction prevented HMGB1 cytoplasmic-nuclear translocation to support transcriptional response to infection. Remarkably, HMGB1 knockdown not only reduced transcriptional response but also slowed virus replication rate, suggesting that HMGB1 also controlled the expression of host factors necessary for DENV replication. Indeed, introducing 29 V to prM increased virus replication rate and transcription of antiviral response genes in both wild-type DENV-3 as well as chimeric DENV-3/-2, the DENV-3 component of TAK-003. Our findings suggest exploiting this interaction to improve immunogenicity and potentially efficacy of current vaccines."],"study_type":["transcription profiling by array"],"species":["Homo sapiens"],"pubmed_title":["Reduced dengue virus pre-membrane protein-HMGB1 interaction activates host cell transcription to attenuate infection","Reduced dengue virus pre-membrane protein-HMGB1 interaction activates host cell transcription to attenuate infection."],"pubmed_authors":["Siriphanitchakorn T, Ooi JSG, Ng WC, Tan HC, Zhang SL, Ng DHL, Yap X, Yee JX, Zheng Q, Tan YT, Ong EZ, Chan KR, Choy MM, Ooi EE.","Kuan Rong Chan","Tanamas Siriphanitchakorn, Justin S. G. Ooi, Wy Ching Ng, Hwee Cheng Tan, Summer L. Zhang, Dorothy H. L. Ng, Xin Yap, Jia Xin Yee, Qiao Zheng, Yi Ting Tan, Eugenia Z. Ong, Kuan Rong Chan, Milly M. Choy, Eng Eong Ooi","Justin Ooi"],"additional_accession":[]},"is_claimable":false,"name":"Transcriptional analysis of primary human monocyte-derived dendritic cells (moDCs) infected with WT and attenuated mutant Dengue virus 2 strains","description":"Primary human monocytes were isolated and differentiated into moDCs. These moDCs were infected with WT Dengue virus 2 and its attenuated mutants (generated using infectious clone construction with site-directed mutagenesis) to better understand the gene expression changes induced by these different attenuated viruses.","dates":{"release":"2026-04-14T00:00:00Z","modification":"2026-05-14T18:45:11.545Z","creation":"2025-11-19T13:30:55.856Z"},"accession":"E-MTAB-16201","cross_references":{"pubmed":["publ-0-4mdx-removable","41702930"],"Biostudies":["E-MTAB-16204","E-MTAB-16202"],"EFO":["EFO_0002768","EFO_0002944","EFO_0003814","EFO_0003813","EFO_0005518","EFO_0003816","EFO_0003815"],"doi":["10.1038/s41541-026-01401-3"]}}