Plasmodium vivax hypnozoites persist in the liver, cause malaria relapse and represent a major challenge to malaria elimination. Our previous transcriptomic study provided a novel molecular framework to enhance our understanding of the hypnozoite biology (Voorberg-van der Wel A, et al., 2017). In this dataset, we identified and characterized the Liver-Specific Protein 2 (LISP2) protein as an early molecular marker of liver stage development. Immunofluorescence analysis of hepatocytes infected with relapsing malaria parasites, in vitro (P. cynomolgi) and in vivo (P. vivax), reveals that LISP2 expression discriminates between dormant hypnozoites and early developing parasites. We further demonstrate that prophylactic drugs selectively kill all LISP2 positive parasites, while LISP2 negative hypnozoites are only sensitive to anti-relapse drug tafenoquine. Our results provide novel biological insights in the initiation of liver stage schizogony and an early marker suitable for the development of drug discovery assays predictive of anti-relapse activity.
- Guglielmo Roma
- Clemens H M Kocken
- Thierry Tidiane Diagana
- Sebastian A Mikolajczak
Funders have no role in the design of the study.
Animal experimentation: Ethics statement included in the method section of the manuscript.
- Urszula Krzych, Walter Reed Army Institute of Research, United States
- Received: November 9, 2018
- Accepted: May 13, 2019
- Accepted Manuscript published: May 16, 2019 (version 1)
© 2019, Gupta et al.
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