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

Cláudia Sá E Cunha1, Britta Nyboer2, Kirsten Heiss2,3

  • 1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.

Proceedings of the National Academy of Sciences of the United States of America
|February 1, 2017
PubMed

Insights

Malaria parasites require exported protein 1 (EXP-1) to bind Apolipoprotein H (ApoH) during liver-stage development. This interaction is crucial for parasite replication and infection progression, offering new targets for malaria prevention.

Area of Science:

  • * Molecular parasitology
  • * Infectious disease research
  • * Host-pathogen interactions

Background:

  • * Malaria parasite liver-stage development involves rapid parasite replication within host hepatocytes.
  • * Parasite development occurs within a specialized compartment called the parasitophorous vacuole (PV).
  • * Understanding host-parasite interactions during this phase is critical for developing effective interventions.

Purpose of the Study:

  • * To investigate the role of the exported protein 1 (EXP-1) in malaria parasite liver-stage development.
  • * To identify and characterize the molecular interaction between EXP-1 and host factors.
  • * To assess the impact of this interaction on intrahepatic parasite replication and disease progression.

Main Methods:

  • * Analysis of the C-terminal region of EXP-1 for host protein binding.
  • * Expression of truncated EXP-1 and Apolipoprotein H (ApoH) in hepatic cells and mouse models.
  • * RNA interference (RNAi) to down-regulate ApoH expression.
  • * Infection studies using genetically modified sporozoites and assessment of liver burden and blood-stage patency.

Main Results:

  • * The C-terminal region of EXP-1 directly binds to host Apolipoprotein H (ApoH).
  • * Disruption of the EXP-1/ApoH interaction via truncated EXP-1 or ApoH down-regulation impaired intrahepatic parasite development.
  • * Mice infected with EXP-1 mutant sporozoites showed reduced liver burden and delayed onset of blood-stage malaria.
  • * This interaction is essential for efficient Plasmodium liver-stage replication and subsequent systemic infection.

Conclusions:

  • * The interaction between Plasmodium EXP-1 and host ApoH is a critical determinant of successful liver-stage development.
  • * This host-parasite molecular interaction represents a potential new target for anti-malarial strategies.
  • * Targeting this interaction could lead to novel approaches for malaria prevention and control.
Keywords:
ApoHEXP-1Plasmodium liver stageshost–parasite interactionmalaria

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