Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion.
Some human malaria Plasmodium falciparum parasites, but not others, also cause disease in Aotus monkeys. To identify the basis for this variation, we crossed two clones that differ in Aotus nancymaae virulence and mapped inherited traits of infectivity to erythrocyte invasion by linkage analysis. A major pathway of invasion was linked to polymorphisms in a putative erythrocyte binding protein, PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent parasite. Conversely, replacements that removed these polymorphisms from PfRH5 converted a virulent progeny clone to a nonvirulent parasite. Further, a proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors.
Hayton
Karen
K
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-8132, USA.
Gaur
Deepak
D
Liu
Anna
A
Takahashi
Jonathan
J
Henschen
Bruce
B
Singh
Subhash
S
Lambert
Lynn
L
Furuya
Tetsuya
T
Bouttenot
Rachel
R
Doll
Michelle
M
Nawaz
Fatima
F
Mu
Jianbing
J
Jiang
Lubin
L
Miller
Louis H
LH
Wellems
Thomas E
TE
D000595:Amino Acid Sequence; D000818:Animals; D016645:Aotidae / Q000469:parasitology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004912:Erythrocytes / Q000469:parasitology*; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D011485:Protein Binding; D016415:Sequence Alignment; D014774:Virulence
D002352:Carrier Proteins; C531020:RH5 protein, Plasmodium falciparum