A Role for Apical Membrane Antigen 1 during Invasion of Hepatocytes byPlasmodium falciparumSporozoites Academic Article uri icon

abstract

  • Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and invade hepatocytes as a first and obligatory step of the parasite life cycle in man. Hepatocyte invasion involves proteins secreted from parasite vesicles called micronemes, the most characterized being the thrombospondin-related adhesive protein (TRAP). Here we investigated the expression and function of another microneme protein recently identified in Plasmodium falciparum sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1 antibodies inhibit sporozoite invasion, suggesting that the protein is involved during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP relocate to the sporozoite surface, where they are proteolytically cleaved, resulting in the shedding of soluble fragments. A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection.

authors

  • Silvie, Olivier
  • Franetich, Jean-François
  • Charrin, Stéphanie
  • Mueller, Markus S
  • Siau, Anthony
  • Bodescot, Myriam
  • Rubinstein, Eric
  • Hannoun, Laurent
  • Charoenvit, Yupin
  • Kocken, Clemens H
  • Thomas, Alan W
  • van Gemert, Geert-Jan
  • Sauerwein, Robert W
  • Blackman, Michael J
  • Anders, Robin F
  • Pluschke, Gerd
  • Mazier, Dominique

publication date

  • March 5, 2004