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Review
. 2023 Aug 22;12(9):1070.
doi: 10.3390/pathogens12091070.

Transfection Models to Investigate Plasmodium vivax-Type Dormant Liver Stage Parasites

Annemarie Voorberg-van der Wel  1 , Anne-Marie Zeeman  1 , Clemens H M Kocken  1
Affiliations
Review

Transfection Models to Investigate Plasmodium vivax-Type Dormant Liver Stage Parasites

Annemarie Voorberg-van der Wel et al. Pathogens. .

Abstract

Plasmodium vivax causes the second highest number of malaria morbidity and mortality cases in humans. Several biological traits of this parasite species, including the formation of dormant stages (hypnozoites) that persist inside the liver for prolonged periods of time, present an obstacle for intervention measures and create a barrier for the elimination of malaria. Research into the biology of hypnozoites requires efficient systems for parasite transmission, liver stage cultivation and genetic modification. However, P. vivax research is hampered by the lack of an in vitro blood stage culture system, rendering it reliant on in vivo-derived, mainly patient, material for transmission and liver stage culture. This has also resulted in limited capability for genetic modification, creating a bottleneck in investigations into the mechanisms underlying the persistence of the parasite inside the liver. This bottleneck can be overcome through optimal use of the closely related and experimentally more amenable nonhuman primate (NHP) parasite, Plasmodium cynomolgi, as a model system. In this review, we discuss the genetic modification tools and liver stage cultivation platforms available for studying P. vivax persistent stages and highlight how their combined use may advance our understanding of hypnozoite biology.

Keywords: Plasmodium cynomolgi; Plasmodium vivax; genetic modification; hypnozoite; liver stage; malaria; transfection.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
P. cynomolgi in vivo and in vitro transfection capabilities. Transgenic parasites can be drug selected in vivo or in vitro. To date, successful transmission of P. cynomolgi has only been described following a monkey passage (broken arrow) and it is not known whether in vitro cultured parasites can be transmitted in the absence of a monkey passage (broken arrow with question mark). Transgenic liver stage parasites, including hypnozoites (upper right-hand side, schematic drawing of a hepatocyte with GFP expressing hypnozoite) can be studied in vitro following sporozoite inoculation of cultured primary hepatocytes.
Figure 2
Figure 2
Access to different stages of the life cycle of P. vivax-type parasites. Stages of the parasite life cycle for which the availability of transgenic parasites has been described are depicted in green; stages that are accessible for experimentation, but that have only been studied using wild-type parasites are depicted in grey. Question marks highlight the current lack of knowledge on the capacity for in vitro cultured parasites to be transmitted without passage through a monkey.
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