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Analysis of Plasmodium falciparum var Genes Expressed in Children from Papua New Guinea

Falk, Nicole ; Kaestli, Mirjam ; Qi, Weihong ; Ott, Michael ; Baea, Kay ; Corteés, Alfred ; Beck, Hans-Peter

In: Journal of Infectious Diseases, 2009, vol. 200, no. 3, p. 347-356

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    Titel
    • Analysis of Plasmodium falciparum var Genes Expressed in Children from Papua New Guinea
    Autor
    • Falk, Nicole. Swiss Tropical Institute, Basel, Switzerland
    • Kaestli, Mirjam. Swiss Tropical Institute, Basel, Switzerland
    • Qi, Weihong. Swiss Tropical Institute, Basel, Switzerland
    • Ott, Michael. F. Hoffmann-La Roche AG, Basel, Switzerland
    • Baea, Kay. Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
    • Corteés, Alfred. Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
    • Beck, Hans-Peter. Swiss Tropical Institute, Basel, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Journal of Infectious Diseases, 2009, vol. 200, no. 3, p. 347-356. The University of Chicago Press
    Andere elektronische Ausgabe
    Klassifikation
    • Gesundheit
    OAI-PMH-ID
    • oai:doc.rero.ch:297195
    Summary
    Background The variable antigen P. falciparum erythrocyte membrane protein-1 (PfEMP1) is a major virulence factor in malaria. A large number of var genes encode PfEMP1, and we hypothesized that a restricted PfEMP1 repertoire determines clinical disease presentation. We conducted a case-control study in Papua New Guinea and analyzed transcribed var genes in naturally infected children. Methods var messenger RNA was isolated from 78 children with asymptomatic, mild, or severe malaria. We prepared complementary DNA from the upstream region into the DBL1α domain and picked, on average, 20 clones for sequencing. Results Twenty-five percent of centrally located var genes were shared between children, whereas only 5% of subtelomeric genes were shared, indicating lower diversity in the former group. Linkage between group B or C var upstream sequences and DBL1α groups was not observed, which impeded prediction by DBL1α analysis. A higher proportion of var group A sequences was detected in symptomatic malaria, and a subgroup of frequently encountered var genes with complex head structure seems to be associated with severe malaria. A subset of var group C genes was frequently expressed in older children with asymptomatic high levels of parasitemia. Conclusion Despite this vast diversity, restricted disease-associated var genes were identified and might be used for innovative interventions based on PfEMP1