Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development

• Verfasst von: Sá e Cunha, Claudia [VerfasserIn]
• Verfasst von: Nyboer, Britta [VerfasserIn]
• Verfasst von: Heiß, Kirsten [VerfasserIn]
• Verfasst von: Wiedtke, Ellen [VerfasserIn]
• Verfasst von: Grimm, Dirk [VerfasserIn]
• Verfasst von: Müller, Ann-Kristin [VerfasserIn]
• Titel: Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development
• Verf.angabe: Cláudia Sá e Cunha, Britta Nyboer, Kirsten Heiss, Margarida Sanches-Vaz, Diana Fontinha, Ellen Wiedtke, Dirk Grimm, Jude Marek Przyborski, Maria M. Mota, Miguel Prudêncio, and Ann-Kristin Mueller
• Umfang: 10 S.
• Fussnoten: Gesehen am 29.05.2018
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC): Proceedings of the National Academy of Sciences of the United States of America
• Jahr Quelle: 2017
• Band/Heft Quelle: 114(2017), 7, S. E1138-E1147
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1606419114
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1575826143

Abstract

The clinically silent intracellular development of Plasmodium parasites in the host liver is a prerequisite for the onset of malaria pathology. Liver stages can be completely eliminated by sterilizing immune responses and are promising targets for urgently needed antimalarial drugs and/or vaccines. The parasite is separated from the host cell cytoplasm by a parasitophorous vacuole (PV). We show that the PV membrane protein exported protein 1 interacts specifically with host Apolipoprotein H. The characterization of this protein-protein interaction revealed an essential role for both molecular partners during intrahepatic parasite growth. Our results improve our understanding of cell-biological aspects of host-pathogen interactions and may also help to develop new strategies to control Plasmodium infections., 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.