# Comparative transcriptomics of Plasmodium vivax strains to understand hypnozoite formation

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2024 · $226,500

## Abstract

PROJECT SUMMARY
Even though 60-85% of Plasmodium vivax (Pv) infections are caused by dormant liver stages, known as
hypnozoites (HZs), the molecular mechanisms that govern dormancy remain largely unknown. Without this
information, new interventions to eliminate HZs cannot be developed, and Pv malaria will continue to cause
substantial morbidity and socioeconomic hardships. The long-term goal of our research program is to understand
the molecular mechanisms that govern HZ dormancy so that these processes can serve as targets for new
therapeutics. The objective of this proposal is to understand how HZs are formed by addressing if Pv sporozoites
are pre-destined to develop into HZs or replicating schizonts (SZs) before or after invading a liver cell. This
information is needed because understanding how HZs are formed may lead to the identification of new
therapeutic approaches to eliminate them. Prior research has attempted to address if sporozoites are already
committed to dormancy prior to invading a liver cell, but the studies have been inconclusive because Pv
sporozoites with fixed, pre-determined fates have not been used. In preliminary studies, our team has overcome
this limitation by optimizing procedures to produce Pv North Korean, Brazil VII, and Chesson sporozoites. We
show that sporozoites from these strains develop into (1) nearly all HZs, (2) virtually no HZs, and (3) a mixture
of HZs and SZs, respectively, after invading primary human hepatocytes in vitro. The characterization of these
strains has provided the necessary technical innovation to determine if Pv sporozoites are pre-destined to
develop into dormant HZs or replicating SZs before or after invading a liver cell. Our central hypothesis is that
the fate of sporozoites is pre-programmed by distinct transcriptional programs that poise sporozoites to develop
into HZs or SZs. The rationale for this hypothesis is based on our preliminary data that these strains consistently
form the same proportions of HZs irrespective of the hepatocyte donor used or multiple passages through the
mosquito; therefore, fate must be pre-programmed in sporozoites. This proposal will test that hypothesis by
pursuing two specific aims. Aim 1 will test the hypothesis that Pv sporozoites are pre-programmed to develop
into HZs prior to hepatocyte invasion while Aim 2 will test the alternative hypothesis that development into a
hypnozoite is determined after hepatocyte invasion. The expected outcomes of this work is the determination of
when a Pv sporozoite commits to becoming a HZ and the molecular programs involved in this process. The
results of these studies will have an important positive impact because they may lead to the identification of new
therapeutic strategies to treat HZs.

## Key facts

- **NIH application ID:** 10988379
- **Project number:** 1R21AI180920-01A1
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Chester J. Joyner
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $226,500
- **Award type:** 1
- **Project period:** 2024-06-07 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988379

## Citation

> US National Institutes of Health, RePORTER application 10988379, Comparative transcriptomics of Plasmodium vivax strains to understand hypnozoite formation (1R21AI180920-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10988379. Licensed CC0.

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