RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver infection

ABSTRACT: The apicomplexan parasites Plasmodium spp. are the causative agents of malaria, a disease that poses a significant global health burden. Plasmodium spp. initiate infection of the human host by transforming and replicating within hepatocytes. Yet, despite the liver stage being a critical step during infection, most transcriptomic studies have focused on more technically accessible stages of the Plasmodium life cycle, limiting our ability to target these parasites to prevent disease. We have conducted an extensive RNA-seq analysis of the Plasmodium berghei liver stage at high-resolution, covering early (2—18 hpi) and mid-stages (24—48 hpi) of the liver stage of infection. Our data revealed hundreds of genes are differentially expressed as early as 2 hours post-infection, and that multiple genes shown to be important for later infection may be upregulated as early as 12 hpi. Using hierarchical clustering along with co-expression analysis, we identified clusters functionally enriched for important liver-stage processes such as interactions with the host cell and redox homeostasis. Furthermore, some of these clusters were highly correlated to the expression of ApiAP2 transcription factors, while showing enrichment of mostly uncharacterized DNA binding motifs hinting at alternative uncharacterized targets during this stage. Our work represents a window into the previously undescribed transcriptome of the early LS upon host cell infection and offers a comprehensive view of the Plasmodium liver stage. Using the tractable organism P. berghei, our dataset provides a blueprint for future studies in the human-infective parasites, P. falciparum and P. vivax.

ORGANISM(S): Homo sapiens Plasmodium berghei

PROVIDER: GSE145731 | GEO | 2020/02/22

REPOSITORIES: GEO