Genetic polymorphism and natural selection of circumsporozoite protein in MyanmarPlasmodium vivax

초록

Background Circumsporozoite surface protein (CSP) of malaria parasites has been recognized as one of the leading vaccine candidates. Clinical trials of vaccines for vivax malaria incorporatingPlasmodium vivaxCSP (PvCSP) have demonstrated their effectiveness in preventing malaria, at least in part. However, genetic diversity ofpvcspin the natural population remains a major concern. Methods A total of 171 blood samples collected from patients infected withPlasmodium vivaxin Myanmar were analysed in this study. Thepvcspwas amplified by polymerase chain reaction, followed by cloning and sequencing. Polymorphic characteristics and natural selection ofpvcsppopulation in Myanmar were analysed using DNASTAR, MEGA6 and DnaSP programs. The polymorphic pattern and natural selection of publicly accessible globalpvcspsequences were also comparatively analysed. Results Myanmarpvcspsequences were divided into two subtypes VK210 and VK247 comprising 143 and 28 sequences, respectively. The VK210 subtypes showed higher levels of genetic diversity and polymorphism than the VK247 subtypes. The N-terminal non-repeat region ofpvcspdisplayed limited genetic variations in the global population. Different patterns of octapeptide insertion (ANKKAEDA in VK210 and ANKKAGDA in VK247) and tetrapeptide repeat motif (GGNA) were identified in the C-terminal region of globalpvcsppopulation. Meanwhile, the central repeat region (CRR) of Myanmar and globalpvcsp, both in VK210 and VK247 variants, was highly polymorphic. The high level of genetic diversity in the CRR has been attributed to the different numbers, types and combinations of peptide repeat motifs (PRMs). Interestingly, 27 and 5 novel PRMs were found in Myanmar VK210 and VK247 variants, respectively. Conclusion Comparative analysis of the globalpvcsppopulation suggests a complex genetic profile ofpvcspin the global population. These results widen understanding of the genetic make-up ofpvcspin the globalP. vivaxpopulation and provide valuable information for the development of a vaccine based on PvCSP.

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