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  • Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite

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    Author(s)
    Stanisic, Danielle I
    Gerrard, John
    Fink, James
    Griffin, Paul M
    Liu, Xue Q
    Sundac, Lana
    Sekuloski, Silvana
    Rodriguez, Ingrid B
    Pingnet, Jolien
    Yang, Yuedong
    Zhou, Yaoqi
    Trenholme, Katharine R
    Wang, Claire YT
    Hackett, Hazel
    Chan, Jo-Anne A
    Langer, Christine
    Hanssen, Eric
    Hoffman, Stephen L
    Beeson, James G
    McCarthy, James S
    Good, Michael F
    Griffith University Author(s)
    Good, Michael F.
    Stanisic, Danielle
    Year published
    2016
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    Abstract
    Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to ...
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    Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo. However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence.
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    Journal Title
    Infection and Immunity
    Volume
    84
    Issue
    9
    DOI
    https://doi.org/10.1128/IAI.00414-16
    Copyright Statement
    © 2016 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Biological sciences
    Other biological sciences not elsewhere classified
    Agricultural, veterinary and food sciences
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/142910
    Collection
    • Journal articles

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