title: Plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface.
abstract: Plasmodium parasites of mammals, including the species that cause malaria in humans, infect the liver first and develop there into clinically silent liver stages. Liver stages grow and ultimately produce thousands of first-generation merozoites, which initiate the erythrocytic cycles causing malaria pathology. Here, we present a Plasmodium protein with a critical function for complete liver stage development. UIS4 (up-regulated in infective sporozoites gene 4) is expressed exclusively in infective sporozoites and developing liver stages, where it localizes to the parasitophorous vacuole membrane. Targeted gene disruption of UIS4 in the rodent model malaria parasite Plasmodium berghei generated knockout parasites that progress through the malaria life cycle until after hepatocyte invasion but are severely impaired in further liver stage development. Immunization with UIS4 knockout sporozoites completely protects mice against subsequent infectious WT sporozoite challenge. Genetically attenuated liver stages may thus induce immune responses, which inhibit subsequent infection of the liver with WT parasites.
authors.affiliation: Department of Parasitology, Heidelberg University School of Medicine, 69120 Heidelberg, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mueller
authors.forename: Nelly
authors.initials: N
authors.lastname: Camargo
authors.forename: Karine
authors.initials: K
authors.lastname: Kaiser
authors.forename: Cathy
authors.initials: C
authors.lastname: Andorfer
authors.forename: Ute
authors.initials: U
authors.lastname: Frevert
authors.forename: Kai
authors.initials: K
authors.lastname: Matuschewski
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D005260:Female; D007114:Immunization; D008099:Liver / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000254:growth & development* / Q000276:immunology; D015800:Protozoan Proteins / Q000502:physiology*; D034101:Sporozoites / Q000276:immunology / Q000502:physiology; D014617:Vacuoles / Q000469:parasitology
chemical_list: D015800:Protozoan Proteins