Plasmodium vivax merozoite surface protein PvMSP-3 beta is radically polymorphic through mutation and large insertions and deletions.

摘要

Plasmodium vivax causes the majority of malaria outside of sub-Saharan Africa and is an important burden for affected countries. The recent spread of drug-resistant P. vivax strains in these countries has led to renewed pressure for the development of a P. vivax vaccine. The complex life cycle of P. vivax presents many potential vaccine targets, but among the most promising candidates are subunits of the surface coat that surrounds the merozoite, the parasite stage that infects erythrocytes and initiates much of the pathology of malaria. Although the genes for several constituents of the P. vivax surface coat have now been cloned and sequenced, little is known about the extent to which these proteins vary between populations, an important consideration in vaccine development. The merozoite surface protein MSP-3 beta is a member of a family of related merozoite surface proteins, all of which contain a central alanine-rich domain that is predicted to form a coiled-coil tertiary structure. We have sequenced the PvMSP-3 beta gene from P. vivax isolates originating in Central and South America, Asia and the Pacific. In this first assessment of PvMSP-3 beta variation between populations, we discovered widespread and significant diversity, mostly within the alanine-rich central region. We observed frequent differences in PvMSP-3 beta gene size, caused by the insertion and/or deletion of several large sequence blocks, as well as numerous single nucleotide polymorphisms and smaller scale insertions and deletions. Despite this high level of sequence diversity, certain physical properties of the encoded protein are maintained, particularly the ability to form coiled-coil tertiary structures, suggesting that although PvMSP-3 beta varies widely, it is under functional constraints. The implications for PvMSP-3 beta function and vaccine development are discussed.