The &ITPlasmodium falciparum &ITtranscriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding &ITvar &ITgenes
AuthorTonkin-Hill, GQ; Trianty, L; Noviyanti, R; Nguyen, HHT; Sebayang, BF; Lampah, DA; Marfurt, J; Cobbold, SA; Rambhatla, JS; McConville, MJ; ...
Source TitlePLOS BIOLOGY
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sCobbold, Simon; McConville, Malcolm; Duffy, Michael; Rogerson, Stephen; Brown, Graham; Papenfuss, Anthony; Nguyen, Thi Hong Hanh; Rambhatla, Janavi Suresh; Day, Karen
AffiliationMedical Biology (W.E.H.I.)
Medicine and Radiology
Clinical School (Royal Melbourne Hospital)
Melbourne School of Population and Global Health
Biochemistry and Molecular Biology
Microbiology and Immunology
School of BioSciences
Document TypeJournal Article
CitationsTonkin-Hill, G. Q., Trianty, L., Noviyanti, R., Nguyen, H. H. T., Sebayang, B. F., Lampah, D. A., Marfurt, J., Cobbold, S. A., Rambhatla, J. S., McConville, M. J., Rogerson, S. J., Brown, G., Day, K. P., Price, R. N., Anstey, N. M., Papenfuss, A. T. & Duffy, M. F. (2018). The &ITPlasmodium falciparum &ITtranscriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding &ITvar &ITgenes. PLOS BIOLOGY, 16 (3), https://doi.org/10.1371/journal.pbio.2004328.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864071
NHMRC Grant codeNHMRC/1007954
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.
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