Extensive polymorphism in the Plasmodium vivax merozoite surface coat protein MSP-3α is limited to specific domains

Abstract

Plasmodium merozoites are covered by a complex coat of surface proteins. Several of the Merozoite Surface Proteins (MSPs) that make up this coat have been proposed as vaccine candidates although some of the MSPs are known to be highly polymorphic. We present here the first survey and analysis of the polymorphism in the recently characterized P. vivax surface protein PvMSP-3alpha. Full length or partial sequences were obtained for the Pvmsp-3alpha gene from isolates originating in Central and South America, Asia and the Pacific. The Pvmsp-3alpha sequence is remarkably diverse, but this extensive diversity is largely restricted to certain domains of the encoded protein. An acidic C-terminal domain and a smaller hydrophilic N-terminus are relatively conserved, while a central domain containing coiled-coil heptad repeats is highly polymorphic and in some isolates of P. vivax is partially deleted. Unlike other MSPs, there is no evidence of allelic families of PvMSP-3alpha gene sequences, and no evidence that certain patterns of polymorphism group within isolates of similar geographical origin. The distribution and nature of polymorphism suggest that there are functional restrictions on mutations in this gene, and have implications for inclusion of PvMSP-3alpha as a candidate in a P. vivax vaccine.

Immunological markers of Plasmodium vivax exposure and immunity: a systematic review and meta-analysis

“…PvMSP-3α is highly polymorphic, with polymorphisms clustered in the N-terminal half of the central alanine-rich coiledcoil domain (Block I repeats, PvMSP-3α RI ) and the less variable C-terminal half of the domain (Block II repeats, PvMSP-3α RII ). By contrast, the extreme N-terminal (PvMSP-3α NT ) and C-terminal (PvMSP-3α CT ) domains are relatively conserved [54].…”

Genetic structures of geographically distinct Plasmodium vivax populations assessed by PCR/RFLP analysis of the merozoite surface protein 3β gene

“…Although PfMSP3 has limited sequence polymorphism (McColl et al, 1994;McColl and Anders, 1997;Huber et al, 1997), PvMSP3α and β genes are highly polymorphic (Rayner et al, 2002(Rayner et al, ,2004Mascorro et al, 2005,Ord et al, 2005. Molecular evolution studies suggest that extensive polymorphism of PvMSP3α is probably generated by intragenic recombinations and maintained by balancing selection (Rayner et al, 2002;Mascorro et al, 2005;Ord et al, 2005).…”

The genetic diversity of Plasmodium vivax: a review

“…PvMsp-3a, similar to PvMsp-1, is very polymorphic and has been used as a genetic marker in population studies of isolates from diverse geographic localities and origins (Bruce et al 1999). Even though PvMsp-3a is very polymorphic, this polymorphism is restricted to the N-terminal, while the C-terminal is well conserved (Rayner et al 2002). Investigation of PvMsp-3b diversity was by cloning and sequencing full-length gene fragments from fifteen P. vivax isolates originating from Asia, South America and the Pacific region.…”