A new look at adenovirus splicing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: MAOSHAN CHEN
PROVIDER: E-GEOD-54583 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:To combat virus infections, which are major human killers, a deeper understanding of how viruses reprogram their hosts to create optimal production of progeny is needed. Most knowledge on the regulation of cellular gene expression during adenovirus infection is derived from studies of mRNA expression. Here, we investigated the changes in cellular protein expression during the late phase of adenovirus type 2 (Ad2) infection of primary human cells by stable isotope labeling in cell culture (SILAC) with subsequent liquid chromatography-high resolution tandem mass spectrometric (LC-MS/MS) analysis using a Q-Exactive Orbitrap instrument. Cells were in-depth evaluated 24 and 36 hours post infection (hpi) and two biological replicates were investigated using swapped labeling. In total, 2648 and 2394 proteins were quantified at 24 and 36 hpi, respectively. Among them, 659 and 645 were deregulated more than 1.6-fold at the two time points, and approximately 80% of them had sustained regulation from 24 to 36 hpi. For the deregulated genes the change in protein expression was compared with that of RNA expression using cDNA sequencing data from the same time points of infection. The comparison revealed a surprisingly low correlation (r = 0.3). Consistency between changes in RNA and protein expression was observed for approximately 30% of the genes, whereas a majority showed either divergent or opposite expression profiles. The deregulated proteins were subjected to pathway and biological function analysis using bioinformatics tools. A surprising observation was that proteins related to carbohydrate metabolism were up-regulated at the protein level but unchanged at the RNA level whereas histone proteins were down-regulated at the protein level but up-regulated at the RNA level. Our results show that regulation of cellular gene expression in the response to viral infection is more complex than hitherto believed and several examples of posttranscriptional regulation of gene expression were observed. The results contribute to our understanding of host cell gene regulation during infection at a deeper level.
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Project description:To combat virus infections, which are major human killers, a deeper understanding of how viruses reprogram their hosts to create optimal production of progeny is needed. Most knowledge on the regulation of cellular gene expression during adenovirus infection is derived from studies of mRNA expression. Here, we investigated the changes in cellular protein expression during the early phase of adenovirus type 2 (Ad2) infection of primary human cells by stable isotope labeling in cell culture (SILAC) with subsequent liquid chromatography-high resolution tandem mass spectrometric (LC-MS/MS) analysis using a Q-Exactive Orbitrap instrument. Cells were in-depth evaluated 6 and 12 hours post infection (hpi) and two biological replicates were investigated using swapped labeling. In total, 2027 and 2150 proteins were quantified at 6 and 12 hpi, respectively. Among them, 431 and 544 were deregulated more than 1.5-fold at the two time points. For the deregulated proteins the change in protein expression was compared with that of late phase of infection (see PXD004095). Pathway analysis showed that De novo purine and pyrimidine biosynthesis, Glycolysis and Cytoskeletal regulation by Rho GTPase pathways are activated early during the infection, while the inactivation of the Integrin signalling pathway starts between 6 and 12 hpi. The transcription factor MYC was predicted to be activated with time, and the phosphopeptide analysis revealed the up-regulation of phosphosites related with glycolysis or cytoskeletal reorganization. These results complement the previous knowledge obtained from transcriptomic data, and show novel and specific aspects of how adenovirus influence host cell gene expression at the protein level.The results contribute to our understanding of host cell gene regulation during infection at a deeper level.
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