title: Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite.
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 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.
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Stanisic
authors.affiliation: Gold Coast University Hospital, Southport, Queensland, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Gerrard
authors.affiliation: Gold Coast University Hospital, Southport, Queensland, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Fink
authors.affiliation: Q-Pharm Pty. Ltd., Herston, Queensland, Australia Department of Infectious Diseases, Mater Health Services and Mater Research, South Brisbane, Queensland, Australia School of Medicine, The University of Queensland, Herston, Queensland, Australia Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Queensland, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Griffin
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
authors.forename: Xue Q
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Gold Coast University Hospital, Southport, Queensland, Australia.
authors.forename: Lana
authors.initials: L
authors.lastname: Sundac
authors.affiliation: Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Queensland, Australia.
authors.forename: Silvana
authors.initials: S
authors.lastname: Sekuloski
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Rodriguez
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
authors.forename: Jolien
authors.initials: J
authors.lastname: Pingnet
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
authors.forename: Yuedong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Queensland, Australia.
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Trenholme
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Centre for Children's Health Research, South Brisbane, Australia.
authors.forename: Claire Y T
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Centre for Children's Health Research, South Brisbane, Australia.
authors.forename: Hazel
authors.initials: H
authors.lastname: Hackett
authors.affiliation: Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
authors.forename: Jo-Anne A
authors.initials: JA
authors.lastname: Chan
authors.affiliation: Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Langer
authors.affiliation: Advanced Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Eric
authors.initials: E
authors.lastname: Hanssen
authors.affiliation: Sanaria Inc., Gaithersburg, Maryland, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.affiliation: School of Medicine, The University of Queensland, Herston, Queensland, Australia Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, University of Queensland, Herston, Queensland, Australia.
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.affiliation: Institute for Glycomics, Griffith University, Southport, Queensland, Australia Michael.Good@griffith.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010271:Parasites / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D010455:Peptides; D015800:Protozoan Proteins; C042968:knob protein, Plasmodium falciparum