Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion

Karen Hayton, Deepak Gaur, Anna Liu, Jonathan Takahashi, Bruce Henschen, Subhash Singh, Lynn Lambert, Tetsuya Furuya, Rachel Bouttenot, Michelle Doll, Fatima Nawaz, Jianbing Mu, Lubin Jiang, Louis H. Miller, Thomas E. Wellems*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)40-51
Number of pages12
JournalCell Host and Microbe
Volume4
Issue number1
DOIs
StatePublished - Jul 17 2008

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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