title: Global selection of Plasmodium falciparum virulence antigen expression by host antibodies.
abstract: Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite. These proteins mediate binding of infected cells to the endothelial lining of blood vessels as a strategy to avoid clearance by the spleen and are major targets of naturally acquired immunity. PfEMP1 is encoded by a large multi-gene family called var. Mutually-exclusive transcriptional switching between var genes allows parasites to escape host antibodies. This study examined in detail the patterns of expression of var in a well-characterized sample of parasites from Kenyan Children. Instead of observing clear inverse relationships between the expression of broad sub-classes of PfEMP1, we found that expression of different PfEMP1 groups vary relatively independently. Parasite adaptation to host antibodies also appears to involve a general reduction in detectable var gene expression. We suggest that parasites switch both between different PfEMP1 variants and between high and low expression states. Such a strategy could provide a means of avoiding immunological detection and promoting survival under high levels of host immunity.
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.|Department of Biochemistry and Chemistry, Pwani University, P.O. Box 195, 80108, Kilifi, Kenya.
authors.forename: Abdirahman I
authors.initials: AI
authors.lastname: Abdi
authors.affiliation: The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, OX3 7DQ, UK.|Centre for Research in Therapeutic Sciences and, Institute for Healthcare Management, Strathmore University, P.O. Box 59857-00200 Nairobi, Kenya.
authors.forename: George M
authors.initials: GM
authors.lastname: Warimwe
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Muthui
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Kivisi
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Kiragu
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.|Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Fegan
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.|Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Bull
mesh_terms: D000906:Antibodies / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology / Q000469:parasitology; D015870:Gene Expression / Q000276:immunology; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology; D013499:Surface Properties
chemical_list: D000906:Antibodies; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum