Abstract
Relapses of Plasmodium dormant liver hypnozoites compromise malaria eradication efforts. New radical cure drugs are urgently needed, yet the vast gap in knowledge of hypnozoite biology impedes drug discovery. We previously unraveled the transcriptome of 6 to 7 day-old P. cynomolgi liver stages, highlighting pathways associated with hypnozoite dormancy (Voorberg-van der Wel et al., 2017). We now extend these findings by transcriptome profiling of 9 to 10 day-old liver stage parasites, thus revealing for the first time the maturation of the dormant stage over time. Although progression of dormancy leads to a 10-fold decrease in transcription and expression of only 840 genes, including genes associated with housekeeping functions, we show that pathways involved in quiescence, energy metabolism and maintenance of genome integrity remain the prevalent pathways active in mature hypnozoites.
Highlights
Plasmodium vivax malaria puts 35% of the world’s population at risk of disease (World Health Organization, 1987)
To gain further understanding of dormancy mechanisms described in hypnozoites at days 6 and 7, we FACS-purified hepatocytes containing GFP-expressing hypnozoites (GFPlow) and liver schizonts (GFPhigh) at later time points, 9 and 10 days after P. cynomolgi M strain sporozoite infection
Given the presence of transcripts of genes involved in schizont maturation and merozoite invasion, we hypothesized and confirmed by RNA fluorescence in situ hybridization (FISH) a contamination of day 10 hypnozoites with schizonts and/or released merozoites
Summary
Plasmodium vivax malaria puts 35% of the world’s population at risk of disease (World Health Organization, 1987). A large barrier to P. vivax eradication is afforded by the parasite’s ability to cause relapsing disease weeks to months or even years after the primary mosquito-mediated infection (White, 2011). This aspect of P. vivax infection is caused by a dormant liver stage form of the parasite, named the hypnozoite. There is a vast gap in knowledge surrounding hypnozoite biology that causes a significant setback in developing a novel radical cure drug that can eliminate hypnozoites Such a drug is urgently needed to aid in malaria eradication because the current radical curative drugs cannot be used in all persons in endemic areas.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
