Discordant expression profile between RNA and protein for the genes involved in immune response network in adenovirus type 2 infected cells

Abstract

AbstractAlternation of cellular genes expressions during Adenovirus type 2 (Ad2) infection in IMR-90 cells was studied using paired-end sequencing and stable isotope labeling of amino acids in cell culture mass spectrometric analysis (SILAC-MS). At transcriptional level, cellular genes involved in different pathways revealed distinct expression profiles. At early phase, the genes involved in regulation of cellular immune response, cellular signaling and cell growth control were among the most deregulated. Later follows, in an orderly fashion, genes involved in cell cycle control, DNA replication and further on genes engaged in RNA processing and protein translation. Comparison of cellular gene expression at transcriptional and posttranscriptional levels revealed low correlation. Here we highlight the genes which expose opposite expression profiles with an emphasis on key factors that play important roles in cellular immune pathways including NFκB, JAK/STAT, caspases and MAVS. Transcription of many of these genes was transiently induced early, but became down-regulated in the late phase. In contrast, their expressions at protein level were up-regulated early and so sustained until late phase of infection. Suppression at the transcriptional level and enhancement at the protein level of immune response genes most likely illustrate counteractions between Ad2 and its host cell.ImportanceOur paper comprises a state of the art quality transcriptomics data set unravelling the alterations in gene expression that take place during different phases of an adenovirus infection. The information allows us to draw conclusion about the cellular pathways that are perturbed by the virus. The data set also provides an important resource for scientists in general for future studies on mechanisms behind host/virus interactions in efforts to design tools for combatting virus infections.Moreover, our paper includes novel proteomics information unravelling an unexpected role of post transcriptional events in cellular gene expression, demonstrating that the current picture of the adenovirus replication cycle is simplified.