Polymorphic patterns of the merozoite surface protein-3 beta in Korean isolates of Plasmodium vivax

Abstract

Background: The merozoite surface protein-3 beta of Plasmodium vivax (PvMSP-3 beta) is one of the candidate antigens for blood stage malaria vaccine development. The polymorphisms in PvMSP-3 beta have been reported in certain P. vivax isolates. However, the diversity of PvMSP-3 beta throughout its global distribution has not been well understood. In this study, the genetic diversity and the effects of natural selection in PvMSP-3 beta among P. vivax Korean isolates were analysed. Methods: Blood samples were collected from 95 patients with vivax malaria in Korea. The region flanking full-length PvMSP-3 beta was amplified by polymerase chain reaction and cloned into a TA cloning vector. The PvMSP-3 beta sequence of each isolate was determined and the polymorphic characteristics and effects of natural selection were analysed using the DNASTAR, MEGA4, and DnaSP programs. Results: Five different subtypes of PvMSP-3 beta were identified based on single nucleotide polymorphisms (SNPs), insertions, and deletions. Although a high level of sequence diversity was observed in the PvMSP-3 beta gene, the coiled-coil tertiary structure of the PvMSP-3 beta protein was well conserved in all of the sequences. The PvMSP-3 beta of Korean isolates is under natural selection. DNA polymerase slippage and intragenic recombination likely contributed to PvMSP-3 beta diversity in Korean P. vivax isolates. Conclusions: The PvMSP-3 beta of Korean P. vivax isolates displayed polymorphisms, with SNPs, insertions and deletions scattered throughout of the gene. These results of parasite heterogeneity are relevant to the development of a PvMSP-3 beta based vaccine against P. vivax and the implementation of malaria control programmes in Korea.