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Evidence for <it>in vitro</it> and <it>in vivo</it> expression of the conserved VAR3 (type 3) <it>plasmodium falciparum</it> erythrocyte membrane protein 1
oleh: Wang Christian W, Lavstsen Thomas, Bengtsson Dominique C, Magistrado Pamela A, Berger Sanne S, Marquard Andrea M, Alifrangis Michael, Lusingu John P, Theander Thor G, Turner Louise
Format: | Article |
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Diterbitkan: | BMC 2012-04-01 |
Deskripsi
<p>Abstract</p> <p>Background</p> <p>Members of the <it>Plasmodium falciparum</it> erythrocyte membrane protein 1 (PfEMP1) adhesion antigen family are major contributors to the pathogenesis of <it>P. falciparum</it> malaria infections. The PfEMP1-encoding <it>var</it> genes are among the most diverse sequences in nature, but three genes, <it>var1, var2csa</it> and <it>var3</it> are found conserved in most parasite genomes. The most severe forms of malaria disease are caused by parasites expressing a subset of antigenically conserved PfEMP1 variants. Thus the ubiquitous and conserved VAR3 PfEMP1 is of particular interest to the research field. Evidence of VAR3 expression on the infected erythrocyte surface has never been presented, and <it>var3</it> genes have been proposed to be transcribed and expressed differently from the rest of the <it>var</it> gene family members.</p> <p>Methods</p> <p>In this study, parasites expressing VAR3 PfEMP1 were generated using anti-VAR3 antibodies and the <it>var</it> transcript and PfEMP1 expression profiles of the generated parasites were investigated. The IgG reactivity by plasma from children living in malaria-endemic Tanzania was tested to parasites and recombinant VAR3 protein. Parasites from hospitalized children were isolated and the transcript level of <it>var3</it> was investigated.</p> <p>Results</p> <p><it>Var3</it> is transcribed and its protein product expressed on the surface of infected erythrocytes. The VAR3-expressing parasites were better recognized by children“s IgG than a parasite line expressing a Group B <it>var</it> gene. Two in 130 children showed increased recognition of parasites expressing VAR3 and to the recombinant VAR3 protein after a malaria episode and the isolated parasites showed high levels of <it>var3</it> transcripts.</p> <p>Conclusions</p> <p>Collectively, the presented data suggest that <it>var3</it> is transcribed and its protein product expressed on the surface of infected erythrocytes in the same manner as seen for other <it>var</it> genes both <it>in vitro</it> and <it>in vivo</it>. Only very few children exhibit seroconversion to VAR3 following a malaria episode requiring hospitalization, supporting the previous conclusion drawn from <it>var3</it> transcript analysis of parasites collected from children hospitalized with malaria, that VAR3 is not associated with severe anaemia or cerebral malaria syndromes in children.</p>