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Diversity of the var gene family of Indonesian Plasmodium falciparum isolates.

ABSTRACT: BACKGROUND: The large polymorphic protein PfEMP1 is encoded by the var gene family. PfEMP1 has been shown to play an important role as cytoadherence ligand on the surface of infected erythrocytes and thereby contributes to the distinct pathogenesis of malaria. The study explored the diversity of the DBL1? and DBL2?-C2 domains of the protein from Indonesian Plasmodium falciparum field isolates. METHODS: Samples of patients with severe and uncomplicated malaria from two different malaria-endemic areas in Indonesia were collected and DNA directly extracted. Dried blood on filter paper was prepared for RNA extraction. PCR amplicons were either cloned and subsequently sequenced or directly sequenced for analysis on nucleotide and amino acid level. Recently published as well as self-designed primers were used for amplification. RESULTS: Blood from eight patients was finally used for analysis. Seventy-one different sequences out of over 500 DBL1? sequenced clones were observed, resulting in an average of 8.9 different DBL1? sequences per isolate. The average DBL1? sequence similarity within isolates was similar to between isolates. Phylogenetic analysis demonstrated no clustering of sequences regarding strain or geographical origin. The DBL1? sequences were analysed by distribution of semi-conserved features (cysteine/PoLV1-4 grouping) and classified into six sequence groups. The DBL1? cys2 type was observed in all expressed sequences in vivo. Expression of certain DBL sequences implied potential involvement in the pathogenesis. As expected, the DBL2?-C2 domains showed high to moderate homology among each other. CONCLUSION: The DBL1? domains of PfEMP1 from clinical Indonesian isolates showed high divergence among same isolates and some similarities with other Asia-Pacific strains. Further investigations of important var gene domains with a larger sample size are required to confirm with statistical significance observed associations with severe malaria in Indonesian samples.

SUBMITTER: Sulistyaningsih E

PROVIDER: S-EPMC3614516 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Diversity of the var gene family of Indonesian Plasmodium falciparum isolates.

Sulistyaningsih Erma E Fitri Loeki E LE Löscher Thomas T Berens-Riha Nicole N

Malaria journal 20130227

<h4>Background</h4>The large polymorphic protein PfEMP1 is encoded by the var gene family. PfEMP1 has been shown to play an important role as cytoadherence ligand on the surface of infected erythrocytes and thereby contributes to the distinct pathogenesis of malaria. The study explored the diversity of the DBL1α and DBL2β-C2 domains of the protein from Indonesian Plasmodium falciparum field isolates.<h4>Methods</h4>Samples of patients with severe and uncomplicated malaria from two different mala ...[more]

PMID: 23446319

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Project description:Background:Plasmodium lactate dehydrogenase (pLDH) is a major target in diagnosing the erythrocytic stage of malaria parasites because it is highly expressed during blood-stage parasites and is distinguished from human LDH. Rapid diagnostic tests (RDTs) for malaria use pLDH as a target antigen; however, genetic variations in pLDH within the natural population threaten the efficacy of pLDH-based RDTs.Methods:Genetic polymorphisms of Plasmodium vivax LDH (PvLDH) and Plasmodium falciparum LDH (PfLDH) in Myanmar isolates were analysed by nucleotide sequencing analysis. Genetic polymorphisms and the natural selection of PvLDH and PfLDH were analysed using DNASTAR, MEGA6, and DnaSP ver. 5.10.00 programs. The genetic diversity and natural selection of global PvLDH and PfLDH were also analysed. The haplotype network of global PvLDH and PfLDH was constructed using NETWORK ver. 5.0.0.3. Three-dimensional structures of PvLDH and PfLDH were built with YASARA Structure ver. 18.4.24 and the impact of mutations on structural change and stability was evaluated with SDM ver. 2, CUPSAT and MAESTROweb.Results:Forty-nine PvLDH and 52 PfLDH sequences were obtained from Myanmar P. vivax and P. falciparum isolates. Non-synonymous nucleotide substitutions resulting in amino acid changes were identified in both Myanmar PvLDH and PfLDH. Amino acid changes were also identified in the global PvLDH and PfLDH populations, but they did not produce structural alterations in either protein. Low genetic diversity was observed in global PvLDH and PfLDH, which may be maintained by a strong purifying selection.Conclusion:This study extends knowledge for genetic diversity and natural selection of global PvLDH and PfLDH. Although amino acid changes were observed in global PvLDH and PfLDH, they did not alter the conformational structures of the proteins. These suggest that PvLDH and PfLDH are genetically well-conserved in global populations, which indicates that they are suitable antigens for diagnostic purpose and attractive targets for drug development.

Dataset Information

Diversity of the var gene family of Indonesian Plasmodium falciparum isolates.

Publications

Diversity of the var gene family of Indonesian Plasmodium falciparum isolates.

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