Genome-wide gene expression profiles throughout human malaria parasite liver stage development

Abstract Plasmodium falciparum (Pf) malaria parasite gene expression during the initial infection phase in the liver is poorly characterized. Using a human liver-chimeric mouse model in conjunction with a fluorescent parasite line (PfNF54CSPGFP), we uncovered the transcriptome of key liver stage (LS) developmental phases, while establishing correlations between clustered gene expression profiles and AP2 developmental transcription factors. This provides insight into transcriptional regulation during LS infection and highlights important LS metabolic and biosynthetic pathways. Furthermore, we compared Pf and P. vivax (Pv) LS transcriptomes, highlighting commonalities, such as countering oxidative stress, but also differences in the context of sexual stage commitment in the liver. We also observed expression of PfEMP1 proteins and the Pf Translocon of Exported Proteins (PTEX) and identified protein candidates that might be exported during LS development. This data will inform biological studies and the search for effective drug targets and vaccines that prevent and treat liver stage infection.