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Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development

Plasmodium falciparum (Pf) is causing the greatest malaria burden, yet the liver stages (LS) of this most important parasite species have remained poorly studied. Here, we used a human liver-chimeric mouse model in combination with a novel fluorescent PfNF54 parasite line (PfNF54(csp)GFP) to isolate...

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Autores principales: Zanghi, Gigliola, Patel, Hardik, Camargo, Nelly, Smith, Jenny L., Bae, Yeji, Flannery, Erika L., Chuenchob, Vorada, Fishbaugher, Matthew E., Mikolajczak, Sebastian A, Roobsoong, Wanlapa, Sattabongkot, Jetsumon, Hayes, Kiera, Vaughan, Ashley M., Kappe, Stefan H. I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9881933/
https://www.ncbi.nlm.nih.gov/pubmed/36711670
http://dx.doi.org/10.1101/2023.01.05.522945
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author Zanghi, Gigliola
Patel, Hardik
Camargo, Nelly
Smith, Jenny L.
Bae, Yeji
Flannery, Erika L.
Chuenchob, Vorada
Fishbaugher, Matthew E.
Mikolajczak, Sebastian A
Roobsoong, Wanlapa
Sattabongkot, Jetsumon
Hayes, Kiera
Vaughan, Ashley M.
Kappe, Stefan H. I.
author_facet Zanghi, Gigliola
Patel, Hardik
Camargo, Nelly
Smith, Jenny L.
Bae, Yeji
Flannery, Erika L.
Chuenchob, Vorada
Fishbaugher, Matthew E.
Mikolajczak, Sebastian A
Roobsoong, Wanlapa
Sattabongkot, Jetsumon
Hayes, Kiera
Vaughan, Ashley M.
Kappe, Stefan H. I.
author_sort Zanghi, Gigliola
collection PubMed
description Plasmodium falciparum (Pf) is causing the greatest malaria burden, yet the liver stages (LS) of this most important parasite species have remained poorly studied. Here, we used a human liver-chimeric mouse model in combination with a novel fluorescent PfNF54 parasite line (PfNF54(csp)GFP) to isolate PfLS-infected hepatocytes and generate transcriptomes that cover the major LS developmental phases in human hepatocytes. RNA-seq analysis of early Pf LS trophozoites two days after infection, revealed a central role of translational regulation in the transformation of the extracellular invasive sporozoite into intracellular LS. The developmental time course gene expression analysis indicated that fatty acid biosynthesis, isoprenoid biosynthesis and iron metabolism are sustaining LS development along with amino acid metabolism and biosynthesis. Countering oxidative stress appears to play an important role during intrahepatic LS development. Furthermore, we observed expression of the variant PfEMP1 antigen-encoding var genes, and we confirmed expression of PfEMP1 protein during LS development. Transcriptome comparison of the late Pf liver stage schizonts with P. vivax (Pv) late liver stages revealed highly conserved gene expression profiles among orthologous genes. A notable difference however was the expression of genes regulating sexual stage commitment. While Pv schizonts expressed markers of sexual commitment, the Pf LS parasites were not sexually committed and showed expression of gametocytogenesis repression factors. Our results provide the first comprehensive gene expression profile of the human malaria parasite Pf LS isolated during in vivo intrahepatocytic development. This data will inform biological studies and the search for effective intervention strategies that can prevent infection.
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spelling pubmed-98819332023-01-28 Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development Zanghi, Gigliola Patel, Hardik Camargo, Nelly Smith, Jenny L. Bae, Yeji Flannery, Erika L. Chuenchob, Vorada Fishbaugher, Matthew E. Mikolajczak, Sebastian A Roobsoong, Wanlapa Sattabongkot, Jetsumon Hayes, Kiera Vaughan, Ashley M. Kappe, Stefan H. I. bioRxiv Article Plasmodium falciparum (Pf) is causing the greatest malaria burden, yet the liver stages (LS) of this most important parasite species have remained poorly studied. Here, we used a human liver-chimeric mouse model in combination with a novel fluorescent PfNF54 parasite line (PfNF54(csp)GFP) to isolate PfLS-infected hepatocytes and generate transcriptomes that cover the major LS developmental phases in human hepatocytes. RNA-seq analysis of early Pf LS trophozoites two days after infection, revealed a central role of translational regulation in the transformation of the extracellular invasive sporozoite into intracellular LS. The developmental time course gene expression analysis indicated that fatty acid biosynthesis, isoprenoid biosynthesis and iron metabolism are sustaining LS development along with amino acid metabolism and biosynthesis. Countering oxidative stress appears to play an important role during intrahepatic LS development. Furthermore, we observed expression of the variant PfEMP1 antigen-encoding var genes, and we confirmed expression of PfEMP1 protein during LS development. Transcriptome comparison of the late Pf liver stage schizonts with P. vivax (Pv) late liver stages revealed highly conserved gene expression profiles among orthologous genes. A notable difference however was the expression of genes regulating sexual stage commitment. While Pv schizonts expressed markers of sexual commitment, the Pf LS parasites were not sexually committed and showed expression of gametocytogenesis repression factors. Our results provide the first comprehensive gene expression profile of the human malaria parasite Pf LS isolated during in vivo intrahepatocytic development. This data will inform biological studies and the search for effective intervention strategies that can prevent infection. Cold Spring Harbor Laboratory 2023-01-05 /pmc/articles/PMC9881933/ /pubmed/36711670 http://dx.doi.org/10.1101/2023.01.05.522945 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Zanghi, Gigliola
Patel, Hardik
Camargo, Nelly
Smith, Jenny L.
Bae, Yeji
Flannery, Erika L.
Chuenchob, Vorada
Fishbaugher, Matthew E.
Mikolajczak, Sebastian A
Roobsoong, Wanlapa
Sattabongkot, Jetsumon
Hayes, Kiera
Vaughan, Ashley M.
Kappe, Stefan H. I.
Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
title Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
title_full Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
title_fullStr Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
title_full_unstemmed Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
title_short Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
title_sort global gene expression of human malaria parasite liver stages throughout intrahepatocytic development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9881933/
https://www.ncbi.nlm.nih.gov/pubmed/36711670
http://dx.doi.org/10.1101/2023.01.05.522945
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