AMA1 and MAEBL are important for Plasmodium falciparum sporozoite infection of the liver
Details
Publication Year 2017-03-31, Volume 19, Issue #9, Page e12754
Journal Title
Cellular Microbiology
Publication Type
Journal Article
Abstract
The malaria sporozoite injected by a mosquito migrates to the liver by traversing host cells. The sporozoite also traverses hepatocytes before invading a terminal hepatocyte and developing into exoerythrocytic forms. Hepatocyte infection is critical for parasite development into merozoites that infect erythrocytes, and the sporozoite is thus an important target for antimalarial intervention. Here, we investigated two abundant sporozoite proteins of the most virulent malaria parasite Plasmodium falciparum and show that they play important roles during cell traversal and invasion of human hepatocytes. Incubation of P. falciparum sporozoites with R1 peptide, an inhibitor of AMA1 that blocks merozoite invasion of erythrocytes, strongly reduced cell traversal activity. Consistent with its inhibitory effect on merozoites, R1 peptide also reduced sporozoite entry into human hepatocytes. The strong but incomplete inhibition prompted us to study the AMA-like protein, MAEBL. MAEBL-deficient P. falciparum sporozoites were severely attenuated for cell traversal activity and hepatocyte entry in vitro and for liver infection in humanized chimeric liver mice. This study shows that AMA1 and MAEBL are important for P. falciparum sporozoites to perform typical functions necessary for infection of human hepatocytes. These two proteins therefore have important roles during infection at distinct points in the lifecycle, including the blood, mosquito and liver stages.
Publisher
Wiley
WEHI Research Division(s)
Infection And Immunity
PubMed ID
28371168
Publisher's Version
https://doi.org/10.1111/cmi.12745
NHMRC Grants
NHMRC/1049811
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-05-02 03:01:35
Last Modified: 2018-10-04 01:34:20
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