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

SUBMITTER: Sa E Cunha C 

PROVIDER: S-EPMC5320984 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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<i>Plasmodium berghei</i> EXP-1 interacts with host Apolipoprotein H during <i>Plasmodium</i> liver-stage development.

Sá E Cunha Cláudia C   Nyboer Britta B   Heiss Kirsten K   Sanches-Vaz Margarida M   Fontinha Diana D   Wiedtke Ellen E   Grimm Dirk D   Przyborski Jude Marek JM   Mota Maria M MM   Prudêncio Miguel M   Mueller Ann-Kristin AK  

Proceedings of the National Academy of Sciences of the United States of America 20170130 7


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 <i>Plasmodium</i> 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 membr  ...[more]

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