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Series GSE84285 Query DataSets for GSE84285
Status Public on Aug 09, 2016
Title Genome-wide analysis of Dengue virus 2 infected cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The goal of this study was to compare the transcriptional profile (RNA-seq) of Dengue virus 2 and mock infected cells at 24 and 36 hours post infection. Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication.
 
Overall design A549 cells where infected with Dengue virus 2 or mock and after 24 and 36 hours post infection mRNA was purified. Then the transcriptional profile of these cells was analyzed using RNA-seq.
 
Contributor(s) De Maio F, Risso G, Iglesias G, Shah P, Pozzi B, Gebhard L, Mammi P, Mancini E, Yanovsky M, Andino R, Krogan N, Srebrow A, Gamarnik A
Citation(s) 27575636
Submission date Jul 12, 2016
Last update date May 15, 2019
Contact name Andrea Gamarnik
E-mail(s) agamarnik@leloir.org.ar
Organization name Fundacion Instituto Leloir
Street address Av. Patricias Argentinas 435
City Ciudad Autonoma de Buenos Aires
ZIP/Postal code C1405BWE
Country Argentina
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (12)
GSM2230822 Dengue virus 24 hs replicate A
GSM2230823 Dengue virus 24 hs replicate B
GSM2230824 Dengue virus 24 hs replicate C
Relations
BioProject PRJNA328591
SRA SRP078309

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84285_bin_counts_24h.xlsx 29.4 Mb (ftp)(http) XLSX
GSE84285_bin_counts_36h.xlsx 29.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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