Transcriptome analysis of alternative splicing in the pathogen life cycle in human foreskin fibroblasts infected with Trypanosoma cruzi

Abstract

AbstractTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease as a zoonotic pathogen. The parasite has been shown to remodel expression in the host transcriptome under different conditions. Although alternative splicing (AS) is involved in virtually every biological function in eukaryotes, including cellular differentiation and responses to immune reactions, host AS events that occur as a result of T. cruzi infection have yet to be explored. In this study, we bioinformatically investigated the transcriptome AS dynamics of T. cruzi (Y strain) infected human foreskin fibroblasts using RNA-Seq data captured over four timepoints (4, 24, 48, and 72 h post infection (hpi)). We identified 1768, 399, 250, and 299 differentially expressed exons (AS exons) at 4, 24, 48, and 72 hpi, respectively, showing that host AS mechanism may have a significant role in the intracellular life cycle of the parasite. We present an exon skipping event in HDAC7, which is a candidate gene that is important in the parasite’s cell cycle. To sum up, this bioinformatics analysis of transcriptome may provide new potential insight into AS regulation in human foreskin fibroblast (HFF) cells infected by T. cruzi and into its implication to the parasite life cycle. Moreover, identified AS genes may provide new potential molecular candidates for improving treatment.