| Autor: |
Sá E Cunha C; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Nyboer B; Parasitology Unit, Centre for Infectious Diseases, Heidelberg University Hospital, D 69120 Heidelberg, Germany., Heiss K; Parasitology Unit, Centre for Infectious Diseases, Heidelberg University Hospital, D 69120 Heidelberg, Germany.; German Centre for Infection Research, D 69120 Heidelberg, Germany., Sanches-Vaz M; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Fontinha D; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Wiedtke E; Centre for Infectious Diseases, Virology, Heidelberg University Hospital, D 69120 Heidelberg, Germany.; BioQuant Institute, University of Heidelberg, D 69120 Heidelberg, Germany., Grimm D; 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., Przyborski JM; Department of Parasitology, Faculty of Biology, Philipps University Marburg, D 35043 Marburg, Germany., Mota MM; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal., Prudêncio M; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal; ann-kristin.mueller@uni-heidelberg.de mprudencio@medicina.ulisboa.pt., Mueller AK; 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. |
| Abstrakt: |
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. Hepatic Plasmodium development 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 successful Plasmodium liver-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 by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies. |
