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Research Article

Antibodies Targeting the PfRH1 Binding Domain Inhibit Invasion of Plasmodium falciparum Merozoites

  • Xiaohong Gao,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Kim Pin Yeo,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Siqi Sharon Aw,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Claudia Kuss,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Jayasree K. Iyer,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Saraswathy Genesan,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Ravikumar Rajamanonmani,

    Affiliation: Division of Structural & Computational Biology, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Julien Lescar,

    Affiliation: Division of Structural & Computational Biology, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Zbynek Bozdech,

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Peter R. Preiser mail

    PRPreiser@ntu.edu.sg

    Affiliation: Division of Genomics & Genetics, School of Biological Sciences, Nanyang Technological University, Singapore

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  • Published: July 11, 2008
  • DOI: 10.1371/journal.ppat.1000104

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Two interesting phenomena, immune evasion and translational repression

Posted by dspeterson on 06 Aug 2008 at 17:25 GMT

This manuscript describes some interesting findings about PfRH1, a member of the RBL family of proteins. The RBLs are thought to play a role in the initial recognition of a target cell, signaling for the subsequent deployment of EBLs that function in junction formation. Unlike the members of the EBL family, the RBLs lack a clearly conserved binding region analogous to the duffy binding-like region of the EBLs (and vars). Here the authors defined the binding region of PfRH1 to a small region of at most 334 aa. Antibodies to the binding region, but not another region of PfRH1 inhibit invasion of parasite lines that invade via a sialic acid dependent pathway. Significantly these antibodies do not affect invasion of a parasite line that has switched to a sialic acid independent invasion pathway, which the authors suggest constitutes an immune evasion mechanism. It will be interesting to determine if hyperimmune sera from endemic regions contains antibodies that recognize the PfRH1 binding region, lending support for this suggestion. Also with the binding region now defined, molecular epidemiological studies can determine whether this region shows evidence of selective pressure.
One intriguing finding is that although PfRH1 transcript levels vary among isolates, levels of mRNA and protein not directly correlate, suggesting a post-transcriptional mechanism at play. This finding stands in contrast to what has been observed for other invasion related proteins, for example Cortes et al. found that in a series of subclonal lines varying transcript levels of eba-140, clag2, and clag3.2 were in accord with protein levels[1]. In Plasmodium translational repression has been described for zygote and ookinete specific proteins, a process mediated by a member of the RNa helicase family[2]. Is it possible that such a mechanism is operating here?

1. Cortes, A., et al., Epigenetic silencing of Plasmodium falciparum genes linked to erythrocyte invasion. PLoS Pathog, 2007. 3(8): p. e107.
2. Mair, G.R., et al., Regulation of sexual development of Plasmodium by translational repression. Science, 2006. 313(5787): p. 667-9.