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The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway

We used a transgenic parasite in which Plasmodium falciparum parasites were genetically modified to express Plasmodium vivax apical membrane antigen 1 (PvAMA1) protein in place of PfAMA1 to study PvAMA1-mediated invasion. In P. falciparum, AMA1 interaction with rhoptry neck protein 2 (RON2) is known...

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Autores principales: Lee, Seong-Kyun, Low, Leanne M., Andersen, John F., Yeoh, Lee M., Valenzuela Leon, Paola Carolina, Drew, Damien R., Doehl, Johannes S. P., Calvo, Eric, Miller, Louis H., Beeson, James G., Gunalan, Karthigayan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910450/
https://www.ncbi.nlm.nih.gov/pubmed/36577076
http://dx.doi.org/10.1073/pnas.2215003120
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author Lee, Seong-Kyun
Low, Leanne M.
Andersen, John F.
Yeoh, Lee M.
Valenzuela Leon, Paola Carolina
Drew, Damien R.
Doehl, Johannes S. P.
Calvo, Eric
Miller, Louis H.
Beeson, James G.
Gunalan, Karthigayan
author_facet Lee, Seong-Kyun
Low, Leanne M.
Andersen, John F.
Yeoh, Lee M.
Valenzuela Leon, Paola Carolina
Drew, Damien R.
Doehl, Johannes S. P.
Calvo, Eric
Miller, Louis H.
Beeson, James G.
Gunalan, Karthigayan
author_sort Lee, Seong-Kyun
collection PubMed
description We used a transgenic parasite in which Plasmodium falciparum parasites were genetically modified to express Plasmodium vivax apical membrane antigen 1 (PvAMA1) protein in place of PfAMA1 to study PvAMA1-mediated invasion. In P. falciparum, AMA1 interaction with rhoptry neck protein 2 (RON2) is known to be crucial for invasion, and PfRON2 peptides (PfRON2p) blocked the invasion of PfAMA1 wild-type parasites. However, PfRON2p has no effect on the invasion of transgenic parasites expressing PvAMA1 indicating that PfRON2 had no role in the invasion of PvAMA1 transgenic parasites. Interestingly, PvRON2p blocked the invasion of PvAMA1 transgenic parasites in a dose-dependent manner. We found that recombinant PvAMA1 domains 1 and 2 (rPvAMA1) bound to reticulocytes and normocytes indicating that PvAMA1 directly interacts with erythrocytes during the invasion, and invasion blocking of PvRON2p may result from it interfering with PvAMA1 binding to erythrocytes. It was previously shown that the peptide containing Loop1a of PvAMA1 (PvAMA1 Loop1a) is also bound to reticulocytes. We found that the Loop1a peptide blocked the binding of PvAMA1 to erythrocytes. PvAMA1 Loop1a has no polymorphisms in contrast to other PvAMA1 loops and may be an attractive vaccine target. We thus present the evidence that PvAMA1 binds to erythrocytes in addition to interacting with PvRON2 suggesting that the P. vivax merozoites may exploit complex pathways during the invasion process.
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spelling pubmed-99104502023-06-28 The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway Lee, Seong-Kyun Low, Leanne M. Andersen, John F. Yeoh, Lee M. Valenzuela Leon, Paola Carolina Drew, Damien R. Doehl, Johannes S. P. Calvo, Eric Miller, Louis H. Beeson, James G. Gunalan, Karthigayan Proc Natl Acad Sci U S A Biological Sciences We used a transgenic parasite in which Plasmodium falciparum parasites were genetically modified to express Plasmodium vivax apical membrane antigen 1 (PvAMA1) protein in place of PfAMA1 to study PvAMA1-mediated invasion. In P. falciparum, AMA1 interaction with rhoptry neck protein 2 (RON2) is known to be crucial for invasion, and PfRON2 peptides (PfRON2p) blocked the invasion of PfAMA1 wild-type parasites. However, PfRON2p has no effect on the invasion of transgenic parasites expressing PvAMA1 indicating that PfRON2 had no role in the invasion of PvAMA1 transgenic parasites. Interestingly, PvRON2p blocked the invasion of PvAMA1 transgenic parasites in a dose-dependent manner. We found that recombinant PvAMA1 domains 1 and 2 (rPvAMA1) bound to reticulocytes and normocytes indicating that PvAMA1 directly interacts with erythrocytes during the invasion, and invasion blocking of PvRON2p may result from it interfering with PvAMA1 binding to erythrocytes. It was previously shown that the peptide containing Loop1a of PvAMA1 (PvAMA1 Loop1a) is also bound to reticulocytes. We found that the Loop1a peptide blocked the binding of PvAMA1 to erythrocytes. PvAMA1 Loop1a has no polymorphisms in contrast to other PvAMA1 loops and may be an attractive vaccine target. We thus present the evidence that PvAMA1 binds to erythrocytes in addition to interacting with PvRON2 suggesting that the P. vivax merozoites may exploit complex pathways during the invasion process. National Academy of Sciences 2022-12-28 2023-01-03 /pmc/articles/PMC9910450/ /pubmed/36577076 http://dx.doi.org/10.1073/pnas.2215003120 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Lee, Seong-Kyun
Low, Leanne M.
Andersen, John F.
Yeoh, Lee M.
Valenzuela Leon, Paola Carolina
Drew, Damien R.
Doehl, Johannes S. P.
Calvo, Eric
Miller, Louis H.
Beeson, James G.
Gunalan, Karthigayan
The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway
title The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway
title_full The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway
title_fullStr The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway
title_full_unstemmed The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway
title_short The direct binding of Plasmodium vivax AMA1 to erythrocytes defines a RON2-independent invasion pathway
title_sort direct binding of plasmodium vivax ama1 to erythrocytes defines a ron2-independent invasion pathway
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910450/
https://www.ncbi.nlm.nih.gov/pubmed/36577076
http://dx.doi.org/10.1073/pnas.2215003120
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