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Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins

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  • 05/14/2025
Type of Material
Authors
    Mariko S. Peterson, Emory UniversityChester J. Joyner, Emory UniversityStacey A. Lapp, Emory UniversityJessica A. Brady, University of GeorgiaJennifer Wood, Emory UniversityMonica Cabrera-Mora, Emory UniversityCelia L Saney, Emory UniversityLuis L. Fonseca, Emory UniversityWayne T. Cheng, University of GeorgiaJianlin Jiang, Emory UniversityStephanie R. Soderberg, Emory UniversityMustafa V. Nural, University of GeorgiaAllison Hankus, Emory UniversityDeepa Machiah, Emory UniversityEbru Karpuzoglu, Emory UniversityJeremy D. DeBarry, University of GeorgiaRabindra Tirouvanziam, Emory UniversityJessica C. Kissinger, University of GeorgiaAlberto Moreno, Emory UniversitySanjeev Gumber, Emory UniversityEberhard Voit, Emory UniversityJuan B. Gutierrez, University of GeorgiaRegina Cordy, Emory UniversityMary Galinski, Emory University
Language
  • English
Date
  • 2022-06-23
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2022 Peterson, Joyner, Lapp, Brady, Wood, Cabrera-Mora, Saney, Fonseca, Cheng, Jiang, Soderberg, Nural, Hankus, Machiah, Karpuzoglu, DeBarry, MaHPIC-Consortium, Tirouvanziam, Kissinger, Moreno, Gumber, Voit, Gutierrez, Cordy and Galinski
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Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 12
Grant/Funding Information
  • This project was funded in part by the National Institute of Allergy and Infectious Diseases; National Institutes of Health, Department of Health and Human Services, which established the MaHPIC [Contract No. HHSN272201200031C; MG], the NIH Office of Research Infrastructure Programs/OD P51OD011132, the Defense Advanced Research Program Agency and the US Army Research Office via a cooperative agreement [Contract No. W911NF16C0008; MG], which funded the Technologies for Host Resilience-Host Acute Models of Malaria to study Experimental Resilience (THoR’s HAMMER) consortium.
Supplemental Material (URL)
Abstract
  • Plasmodium knowlesi poses a health threat throughout Southeast Asian communities and currently causes most cases of malaria in Malaysia. This zoonotic parasite species has been studied in Macaca mulatta (rhesus monkeys) as a model for severe malarial infections, chronicity, and antigenic variation. The phenomenon of Plasmodium antigenic variation was first recognized during rhesus monkey infections. Plasmodium-encoded variant proteins were first discovered in this species and found to be expressed at the surface of infected erythrocytes, and then named the Schizont-Infected Cell Agglutination (SICA) antigens. SICA expression was shown to be spleen dependent, as SICA expression is lost after P. knowlesi is passaged in splenectomized rhesus. Here we present data from longitudinal P. knowlesi infections in rhesus with the most comprehensive analysis to date of clinical parameters and infected red blood cell sequestration in the vasculature of tissues from 22 organs. Based on the histopathological analysis of 22 tissue types from 11 rhesus monkeys, we show a comparative distribution of parasitized erythrocytes and the degree of margination of the infected erythrocytes with the endothelium. Interestingly, there was a significantly higher burden of parasites in the gastrointestinal tissues, and extensive margination of the parasites along the endothelium, which may help explain gastrointestinal symptoms frequently reported by patients with P. knowlesi malarial infections. Moreover, this margination was not observed in splenectomized rhesus that were infected with parasites not expressing the SICA proteins. This work provides data that directly supports the view that a subpopulation of P. knowlesi parasites cytoadheres and sequesters, likely via SICA variant antigens acting as ligands. This process is akin to the cytoadhesive function of the related variant antigen proteins, namely Erythrocyte Membrane Protein-1, expressed by Plasmodium falciparum.
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Keywords
Research Categories
  • Biology, Virology
  • Health Sciences, Pathology

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