The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes.
Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the p...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-03-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.2004328 |
| _version_ | 1811177220477026304 |
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| author | Gerry Q Tonkin-Hill Leily Trianty Rintis Noviyanti Hanh H T Nguyen Boni F Sebayang Daniel A Lampah Jutta Marfurt Simon A Cobbold Janavi S Rambhatla Malcolm J McConville Stephen J Rogerson Graham V Brown Karen P Day Ric N Price Nicholas M Anstey Anthony T Papenfuss Michael F Duffy |
| author_facet | Gerry Q Tonkin-Hill Leily Trianty Rintis Noviyanti Hanh H T Nguyen Boni F Sebayang Daniel A Lampah Jutta Marfurt Simon A Cobbold Janavi S Rambhatla Malcolm J McConville Stephen J Rogerson Graham V Brown Karen P Day Ric N Price Nicholas M Anstey Anthony T Papenfuss Michael F Duffy |
| author_sort | Gerry Q Tonkin-Hill |
| collection | DOAJ |
| description | Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients. The transcriptomes of 19 parasite isolates associated with severe malaria indicated that these parasites had decreased glycolysis without activation of compensatory pathways; altered chromatin structure and probably transcriptional regulation through decreased histone methylation; reduced surface expression of PfEMP1; and down-regulated expression of multiple chaperone proteins. Our RNAseq also identified novel associations between disease severity and PfEMP1 transcripts, domains, and smaller sequence segments and also confirmed all previously reported associations between expressed PfEMP1 sequences and severe disease. These findings will inform efforts to identify vaccine targets for severe malaria and also indicate how parasites adapt to-or are selected by-the host environment in severe malaria. |
| first_indexed | 2024-04-10T22:59:08Z |
| format | Article |
| id | doaj.art-766173a9dd9848f58612c42c3709143b |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-10T22:59:08Z |
| publishDate | 2018-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-766173a9dd9848f58612c42c3709143b2023-01-14T05:30:50ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852018-03-01163e200432810.1371/journal.pbio.2004328The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes.Gerry Q Tonkin-HillLeily TriantyRintis NoviyantiHanh H T NguyenBoni F SebayangDaniel A LampahJutta MarfurtSimon A CobboldJanavi S RambhatlaMalcolm J McConvilleStephen J RogersonGraham V BrownKaren P DayRic N PriceNicholas M AnsteyAnthony T PapenfussMichael F DuffyWithin the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients. The transcriptomes of 19 parasite isolates associated with severe malaria indicated that these parasites had decreased glycolysis without activation of compensatory pathways; altered chromatin structure and probably transcriptional regulation through decreased histone methylation; reduced surface expression of PfEMP1; and down-regulated expression of multiple chaperone proteins. Our RNAseq also identified novel associations between disease severity and PfEMP1 transcripts, domains, and smaller sequence segments and also confirmed all previously reported associations between expressed PfEMP1 sequences and severe disease. These findings will inform efforts to identify vaccine targets for severe malaria and also indicate how parasites adapt to-or are selected by-the host environment in severe malaria.https://doi.org/10.1371/journal.pbio.2004328 |
| spellingShingle | Gerry Q Tonkin-Hill Leily Trianty Rintis Noviyanti Hanh H T Nguyen Boni F Sebayang Daniel A Lampah Jutta Marfurt Simon A Cobbold Janavi S Rambhatla Malcolm J McConville Stephen J Rogerson Graham V Brown Karen P Day Ric N Price Nicholas M Anstey Anthony T Papenfuss Michael F Duffy The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. PLoS Biology |
| title | The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. |
| title_full | The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. |
| title_fullStr | The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. |
| title_full_unstemmed | The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. |
| title_short | The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes. |
| title_sort | plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen encoding var genes |
| url | https://doi.org/10.1371/journal.pbio.2004328 |
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