Analysis of Plasmodium falciparum var genes expressed in children from Papua New Guinea

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

    Research output: Contribution to journalArticle

    Abstract

    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 PfEMPl, 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 DBL1? 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 DBL1? groups was not observed, which impeded prediction by DBL1? 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. � 2009 by the Infectious Diseases Society of America. All rights reserved.
    Original languageEnglish
    Pages (from-to)347-356
    Number of pages10
    JournalJournal of Infectious Diseases
    Volume200
    Issue number3
    Publication statusPublished - 2009

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    Falk, N., Kaestli, M., Qi, W., Ott, M., Baea, K., Cortes, A., & Beck, H-P. (2009). Analysis of Plasmodium falciparum var genes expressed in children from Papua New Guinea. Journal of Infectious Diseases, 200(3), 347-356.