title: The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites.
abstract: Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence.
authors.affiliation: Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern 3012, Switzerland.
authors.forename: Mariana
authors.identifier: 0000-0001-6987-6789
authors.initials: M
authors.lastname: De Niz
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Ullrich
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Arlett
authors.initials: A
authors.lastname: Heiber
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Blancke Soares
authors.affiliation: Institute of Zoology, Universtity of Hamburg, 20146 Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pick
authors.affiliation: Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lyck
authors.affiliation: Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.
authors.forename: Derya
authors.initials: D
authors.lastname: Keller
authors.affiliation: Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern 3012, Switzerland.
authors.forename: Gesine
authors.initials: G
authors.lastname: Kaiser
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Monica
authors.initials: M
authors.lastname: Prado
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Flemming
authors.affiliation: ICREA at ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona and Institut d'Investigació Germans Trias i Pujol (IGTP). Ctra. de Can Ruti. Camí de les Escoles, s/n, 08916 Badalona, Spain.
authors.forename: Hernando
authors.initials: H
authors.lastname: Del Portillo
authors.affiliation: Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.affiliation: Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Heussler
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, 20359 Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Spielmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D010802:Phylogeny; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014774:Virulence / Q000235:genetics
chemical_list: D018955:CD36 Antigens; D015800:Protozoan Proteins