A Role for Apical Membrane Antigen 1 During Invasion of Hepatocytes by Plasmodium falciparum Sporozoites

• Main Authors: Silvie, Olivier, Franetich, Jean-Francois, Charrin, Stephanie, Mueller, Markus S, Siau, Anthony, Bodescot, Myriam, Rubinstein, Eric, Hannoun, Laurent, Charoenvit, Yupin, Kocken, Clemens H
• Format: Report
• Language: English
• Subjects: ANTIGENS; CELLS(BIOLOGY); CULICIDAE; CYTOLOGY; FOREIGN REPORTS; FRAGMENTS; FRANCE; HEPATOCYTES; INFECTIOUS DISEASES; LIFE CYCLES; LIVER; Medicine and Medical Research; MEMBRANES(BIOLOGY); Microbiology; PARASITES; PLASMODIUM FALCIPARUM; PROTEINS; REPRINTS; SECRETION; SOLUBILITY; SPOROZOITES; THROMBOSPONDIN

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. Pub. in the Journal of Biological Chemistry, v279 n10, p9490-9496, 5 Mar 2004.