Single amino acid substitution in Plasmodium yoelii erythrocyte ligand determines its localization and controls parasite virulence

Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7167-72. doi: 10.1073/pnas.0811313106. Epub 2009 Apr 3.


The major virulence determinant of the rodent malaria parasite, Plasmodium yoelii, has remained unresolved since the discovery of the lethal line in the 1970s. Because virulence in this parasite correlates with the ability to invade different types of erythrocytes, we evaluated the potential role of the parasite erythrocyte binding ligand, PyEBL. We found 1 amino acid substitution in a domain responsible for intracellular trafficking between the lethal and nonlethal parasite lines and, furthermore, that the intracellular localization of PyEBL was distinct between these lines. Genetic modification showed that this substitution was responsible not only for PyEBL localization but also the erythrocyte-type invasion preference of the parasite and subsequently its virulence in mice. This previously unrecognized mechanism for altering an invasion phenotype indicates that subtle alterations of a malaria parasite ligand can dramatically affect host-pathogen interactions and malaria virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / genetics
  • Amino Acids / metabolism*
  • Animals
  • Erythrocytes / metabolism*
  • Ligands
  • Mice
  • Microscopy, Immunoelectron
  • Molecular Sequence Data
  • Plasmodium yoelii / genetics
  • Plasmodium yoelii / metabolism*
  • Plasmodium yoelii / pathogenicity*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Virulence


  • Amino Acids
  • Ligands
  • Protozoan Proteins

Associated data

  • GENBANK/AB430781
  • GENBANK/AB430782
  • GENBANK/AB430783
  • GENBANK/AB430784
  • GENBANK/AB430785
  • GENBANK/AB430786
  • GENBANK/AB430787
  • GENBANK/AB430788
  • GENBANK/AB430789