title: Molecular mechanism of host specificity in Plasmodium falciparum infection: role of circumsporozoite protein.
abstract: Plasmodium falciparum sporozoites invade liver cells in humans and set the stage for malaria infection. Circumsporozoite protein (CSP), a predominant surface antigen on sporozoite surface, has been associated with the binding and invasion of liver cells by the sporozoites. Although CSP across the Plasmodium genus has homology and conserved structural organization, infection of a non-natural host by a species is rare. We investigated the role of CSP in providing the host specificity in P. falciparum infection. CSP from P. falciparum, P. gallinaceum, P. knowlesi, and P. yoelii species representing human, avian, simian, and rodent malaria species were recombinantly expressed, and the proteins were purified to homogeneity. The recombinant proteins were evaluated for their capacity to bind to human liver cell line HepG2 and to prevent P. falciparum sporozoites from invading these cells. The proteins showed significant differences in the binding and sporozoite invasion inhibition activity. Differences among proteins directly correlate with changes in the binding affinity to the sporozoite receptor on liver cells. P. knowlesi CSP (PkCSP) and P. yoelii CSP (PyCSP) had 4,790- and 17,800-fold lower affinity for heparin in comparison to P. falciparum CSP (PfCSP). We suggest that a difference in the binding affinity for the liver cell receptor is a mechanism involved in maintaining the host specificity by the malaria parasite.
authors.affiliation: Growth and Development Section, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Dharmendar
authors.initials: D
authors.lastname: Rathore
authors.forename: Sybil C L
authors.initials: SC
authors.lastname: Hrstka
authors.forename: John B
authors.initials: JB
authors.lastname: Sacci
authors.forename: Patricia
authors.initials: P
authors.lastname: De la Vega
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Sanjai
authors.initials: S
authors.lastname: Kumar
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McCutchan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D019763:Heparin Lyase / Q000494:pharmacology; D006790:Host-Parasite Interactions; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan; D019763:Heparin Lyase