Molecular Evolution of PvMSP3α Block II in Plasmodium vivax from Diverse Geographic Origins.

Bhavna Gupta,Ananias A Escalante,B P Niranjan Reddy,Liwang Cui,Jeeraphat Sirichaisinthop,Jetsumon Sattabongkot,Guiyun Yan,Qi Fan,Luzia Helena Carvalho

doi:10.1371/journal.pone.0135396

Abstract

Block II of Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is conserved and has been proposed as a potential candidate for a malaria vaccine. The present study aimed to compare sequence diversity in PvMSP3a block II at a local microgeographic scale in a village as well as from larger geographic regions (countries and worldwide). Blood samples were collected from asymptomatic carriers of P. vivax in a village at the western border of Thailand and PvMSP3α was amplified and sequenced. For population genetic analysis, 237 PvMSP3α block II sequences from eleven P. vivax endemic countries were analyzed. PvMSP3α sequences from 20 village-level samples revealed two length variant types with one type containing a large deletion in block I. In contrast, block II was relatively conserved; especially, some non-synonymous mutations were extensively shared among 11 parasite populations. However, the majority of the low-frequency synonymous variations were population specific. The conserved pattern of nucleotide diversity in block II sequences was probably due to functional/structural constraints, which were further supported by the tests of neutrality. Notably, a small region in block II that encodes a predicted B cell epitope was highly polymorphic and showed signs of balancing selection, signifying that this region might be influenced by the immune selection and may serve as a starting point for designing multi-antigen/stage epitope based vaccines against this parasite.

Highlights

Vaccine is a long-term hope to combat malaria—a major infectious disease responsible for more than half a million deaths annually around the world
To investigate the genetic diversity of Plasmodium vivax merozoite surface protein 3α (PvMSP3α) gene on a microgeographic scale, we collected P. vivax samples from asymptomatic carriers in a small village Suan Oi (~500 residents) in western Thailand (Fig 1A) during mass blood surveys conducted in this area
We further investigated the worldwide extent of genetic diversity in a total of 237 sequences of PvMSP3α block II from 11 parasite populations

Summary

Introduction

Vaccine is a long-term hope to combat malaria—a major infectious disease responsible for more than half a million deaths annually around the world. Vaccine research has been largely focused on Plasmodium falciparum—a species responsible for the majority of malaria-related deaths. P. vivax is the most widespread human malaria parasite and it causes 50–70 million infections annually [5]. This co-called ‘benign tertian’ malaria parasite has been increasingly recognized as the cause of significant morbidity and mortality. The changing malaria epidemiology worldwide with increasing proportions of P. vivax malaria further highlights the difficulty for controlling this parasite and emphasizes the need to develop integrated control strategies including vaccine for this parasite [6]

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Conclusion