title: Plasmodium bergheiEXP-1 interacts with host Apolipoprotein H duringPlasmodiumliver-stage development.
abstract: The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. HepaticPlasmodiumdevelopment occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite's hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successfulPlasmodiumliver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wild-type parasites. This study identifies a host-parasite protein interaction during the hepatic stage of infection byPlasmodiumparasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Sá E Cunha
authors.affiliation: Parasitology Unit, Centre for Infectious Diseases, Heidelberg University Hospital, D 69120 Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Nyboer
authors.affiliation: Parasitology Unit, Centre for Infectious Diseases, Heidelberg University Hospital, D 69120 Heidelberg, Germany.|German Centre for Infection Research, D 69120 Heidelberg, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Heiss
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Sanches-Vaz
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Fontinha
authors.affiliation: Centre for Infectious Diseases, Virology, Heidelberg University Hospital, D 69120 Heidelberg, Germany.|BioQuant Institute, University of Heidelberg, D 69120 Heidelberg, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Wiedtke
authors.affiliation: German Centre for Infection Research, D 69120 Heidelberg, Germany.|Centre for Infectious Diseases, Virology, Heidelberg University Hospital, D 69120 Heidelberg, Germany.|BioQuant Institute, University of Heidelberg, D 69120 Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Grimm
authors.affiliation: Department of Parasitology, Faculty of Biology, Philipps University Marburg, D 35043 Marburg, Germany.
authors.forename: Jude Marek
authors.initials: JM
authors.lastname: Przyborski
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; ann-kristin.mueller@uni-heidelberg.de mprudencio@medicina.ulisboa.pt.
authors.forename: Miguel
authors.initials: M
authors.lastname: Prudêncio
authors.affiliation: Parasitology Unit, Centre for Infectious Diseases, Heidelberg University Hospital, D 69120 Heidelberg, Germany; ann-kristin.mueller@uni-heidelberg.de mprudencio@medicina.ulisboa.pt.|German Centre for Infection Research, D 69120 Heidelberg, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mueller
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D015536:Down-Regulation; D017125:Genes, Protozoan; D057809:HEK293 Cells; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017384:Sequence Deletion; D034101:Sporozoites / Q000502:physiology; D014617:Vacuoles / Q000469:parasitology; D053482:beta 2-Glycoprotein I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; D034741:RNA, Small Interfering; D053482:beta 2-Glycoprotein I
keywords: ApoH; EXP-1; Plasmodium liver stages; host–parasite interaction; malaria