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Differential PfEMP1 Expression Is Associated with Cerebral Malaria Pathology

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Smith, Joe, Tembo, Dumizulu L., Nyoni, Benjamin, Murikoli, Rekah V., Mukaka, Mavuto, Milner, Danny A., Berriman, Matthew, Rogerson, Stephen J., Taylor, Terrie E., Molyneux, Malcolm E, Mandala, Wilson L., Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 and Montgomery, Jacqui (2014) 'Differential PfEMP1 Expression Is Associated with Cerebral Malaria Pathology'. PLoS Pathogens, Vol 10, Issue 12, e1004537.

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Abstract

Plasmodium falciparum is unique among human malarias in its ability to sequester in post-capillary venules of host organs. The main variant antigens implicated are the P. falciparum erythrocyte membrane protein 1 (PfEMP1), which can be divided into three major groups (A–C). Our study was a unique examination of sequestered populations of parasites for genetic background and expression of PfEMP1 groups. We collected post-mortem tissue from twenty paediatric hosts with pathologically different forms of cerebral malaria (CM1 and CM2) and parasitaemic controls (PC) to directly examine sequestered populations of parasites in the brain, heart and gut. Use of two different techniques to investigate this question produced divergent results. By quantitative PCR, group A var genes were upregulated in all three organs of CM2 and PC cases. In contrast, in CM1 infections displaying high levels of sequestration but negligible vascular pathology, there was high expression of group B var. Cloning and sequencing of var transcript tags from the same samples indicated a uniformly low expression of group A-like var. Generally, within an organ sample, 1–2 sequences were expressed at dominant levels. 23% of var tags were detected in multiple patients despite the P. falciparum infections being genetically distinct, and two tags were observed in up to seven hosts each with high expression in the brains of 3–4 patients. This study is a novel examination of the sequestered parasites responsible for fatal cerebral malaria and describes expression patterns of the major cytoadherence ligand in three organ-derived populations and three pathological states.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.ppat.1004537
Depositing User: Lynn Roberts-Maloney
Date Deposited: 17 Jun 2015 08:34
Last Modified: 17 Jul 2020 10:58
URI: https://archive.lstmed.ac.uk/id/eprint/5211

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