AI Article Synopsis

  • The dormant liver stage of the malaria parasite Plasmodium vivax, known as hypnozoites, complicates efforts to control and eradicate malaria due to their poorly understood molecular makeup.
  • Researchers utilized advanced techniques to produce the first transcriptome of these hypnozoites, isolating them from infected monkey liver cells and optimizing RNA sequencing methods.
  • The study identified 120 differentially expressed transcripts in hypnozoites compared to dividing liver stages and highlighted potential molecular markers and regulatory mechanisms important for the hypnozoite's dormant state.

Article Abstract

Dormant liver stage forms (hypnozoites) of the malaria parasite Plasmodium vivax present major hurdles to control and eradicate infection. Despite major research efforts, the molecular composition of hypnozoites remains ill defined. Here, we applied a combination of state-of-the-art technologies to generate the first transcriptome of hypnozoites. We developed a robust laser dissection microscopy protocol to isolate individual Plasmodium cynomolgi hypnozoites and schizonts from infected monkey hepatocytes and optimized RNA-seq analysis to obtain the first transcriptomes of these stages. Comparative transcriptomic analysis identified 120 transcripts as being differentially expressed in the hypnozoite stage relative to the dividing liver schizont, with 69 and 51 mRNAs being up- or down-regulated, respectively, in the hypnozoites. This lead to the identification of potential markers of commitment to and maintenance of the dormant state of the hypnozoite including three transcriptional regulators of the ApiAP2 family, one of which is unique to P. cynomolgi and P. vivax, and the global translational repressor, eIF2a kinase eIK2, all of which are upregulated in the hypnozoite. Together, this work not only provides a primary experimentally-derived list of molecular markers of hypnozoites but also identifies transcriptional and posttranscriptional regulation of gene expression as potentially being key to establishing and maintaining quiescence.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516136PMC
http://dx.doi.org/10.1111/cmi.12735DOI Listing

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