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Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of immune targets, which play a central role in the host-parasite interaction by binding to various host molecules. They are encoded by a diverse family of genes called var, of which there are approximately 60 copies in each parasite genome. In sub-Saharan Africa, although P. falciparum infection occurs throughout life, severe malarial disease tends to occur only in childhood. This could potentially be explained if (i) PfEMP1 variants differ in their capacity to support pathogenesis of severe malaria and (ii) this capacity is linked to the likelihood of each molecule being recognized and cleared by naturally acquired antibodies. Here, in a study of 217 Kenyan children with malaria, we show that expression of a group of var genes "cys2," containing a distinct pattern of cysteine residues, is associated with low host immunity. Expression of cys2 genes was associated with parasites from young children, those with severe malaria, and those with a poorly developed antibody response to parasite-infected erythrocyte surface antigens. Cys-2 var genes form a minor component of all genomic var repertoires analyzed to date. Therefore, the results are compatible with the hypothesis that the genomic var gene repertoire is organized such that PfEMP1 molecules that confer the most virulence to the parasite tend also to be those that are most susceptible to the development of host immunity. This may help the parasite to adapt effectively to the development of host antibodies through modification of the host-parasite relationship.

Original publication

DOI

10.1073/pnas.0907590106

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

22/12/2009

Volume

106

Pages

21801 - 21806

Addresses

Kenya Medical Research Institute-Wellcome Trust Research Programme, 80108 Kilifi, Kenya.

Keywords

Animals, Antibodies, Protozoan, Child, Preschool, Genes, Protozoan, Host-Pathogen Interactions, Humans, Infant, Likelihood Functions, Malaria, Falciparum, Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Transport Proteins, Plasmodium falciparum, Protozoan Proteins, Severity of Illness Index