On the Evolution and Function of Plasmodium vivax Reticulocyte Binding Surface Antigen (pvrbsa)

Título traducido de la contribución: Sobre la evolución y función del antígeno de superficie de unión de reticulocitos Plasmodium vivax (pvrbsa)

Paola Andrea Camargo-Ayala, Diego Garzón-Ospina, Darwin Andrés Moreno-Pérez, Laura Alejandra Ricaurte-Contreras, Oscar Noya, Manuel A Patarroyo

Resultado de la investigación: Contribución a RevistaArtículo

Resumen

La proteína de la CSPO está codificada por un gen descrito en la especie Plasmodium que tiene tropismo para los reticulocitos. Dado que esta proteína es antigénica en las infecciones naturales y puede unirse a las células diana, se ha propuesto como candidato potencial para una vacuna anti-Plasmodium vivax. Sin embargo, la diversidad genética (un desafío que debe ser superado para asegurar un diseño de vacuna completamente efectivo) no ha sido descrita en este lugar. Del mismo modo, no se han determinado las regiones mínimas de mediación de la interacción entre parásitos y huéspedes específicos. Por eso se describe la historia evolutiva del gen rbsa, así como la diversidad genética de P. vivax rbsa (pvrbsa) y la adhesión del parásito a los reticulocitos en regiones específicas. A diferencia de lo que se ha informado anteriormente, la rbsa también estaba presente en varias especies de parásitos pertenecientes al clado del mono-malaria; también se encontraron paralogs en los parásitos Plasmodium que invaden los reticulocitos. El pvrbsa locus tenía menos diversidad que otras proteínas de superficie de merozoito, donde la selección natural y la recombinación eran las principales fuerzas evolutivas implicadas en causar el polimorfismo observado. El extremo N-terminal (PvRBSA-A) se conservó y bajo restricción funcional; en consecuencia, se expresó como proteína recombinante para ensayos de unión. Este fragmento de proteína se une a los reticulocitos mientras que el C-terminal, incluido en el PvRBSA-B recombinante (que no estaba bajo restricción funcional), no lo hizo. Interesantemente, dos péptidos derivados de PvRBSA-A fueron capaces de inhibir la unión de proteínas a los reticulocitos. Péptidos específicos conservados y funcionalmente importantes dentro de PvRBSA-A podrían ser considerados al diseñar una vacuna completamente efectiva contra P. vivax.
Idioma originalEnglish (US)
Páginas (desde-hasta)372
PublicaciónFrontiers in Genetics
Volumen9
DOI
EstadoPublished - sep 10 2018
Publicado de forma externa

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Camargo-Ayala, Paola Andrea ; Garzón-Ospina, Diego ; Moreno-Pérez, Darwin Andrés ; Ricaurte-Contreras, Laura Alejandra ; Noya, Oscar ; Patarroyo, Manuel A. / On the Evolution and Function of Plasmodium vivax Reticulocyte Binding Surface Antigen (pvrbsa). En: Frontiers in Genetics. 2018 ; Vol. 9. pp. 372.
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title = "On the Evolution and Function of Plasmodium vivax Reticulocyte Binding Surface Antigen (pvrbsa)",
abstract = "The RBSA protein is encoded by a gene described in Plasmodium species having tropism for reticulocytes. Since this protein is antigenic in natural infections and can bind to target cells, it has been proposed as a potential candidate for an anti-Plasmodium vivax vaccine. However, genetic diversity (a challenge which must be overcome for ensuring fully effective vaccine design) has not been described at this locus. Likewise, the minimum regions mediating specific parasite-host interaction have not been determined. This is why the rbsa gene's evolutionary history is being here described, as well as the P. vivax rbsa (pvrbsa) genetic diversity and the specific regions mediating parasite adhesion to reticulocytes. Unlike what has previously been reported, rbsa was also present in several parasite species belonging to the monkey-malaria clade; paralogs were also found in Plasmodium parasites invading reticulocytes. The pvrbsa locus had less diversity than other merozoite surface proteins where natural selection and recombination were the main evolutionary forces involved in causing the observed polymorphism. The N-terminal end (PvRBSA-A) was conserved and under functional constraint; consequently, it was expressed as recombinant protein for binding assays. This protein fragment bound to reticulocytes whilst the C-terminus, included in recombinant PvRBSA-B (which was not under functional constraint), did not. Interestingly, two PvRBSA-A-derived peptides were able to inhibit protein binding to reticulocytes. Specific conserved and functionally important peptides within PvRBSA-A could thus be considered when designing a fully-effective vaccine against P. vivax.",
author = "Camargo-Ayala, {Paola Andrea} and Diego Garz{\'o}n-Ospina and Moreno-P{\'e}rez, {Darwin Andr{\'e}s} and Ricaurte-Contreras, {Laura Alejandra} and Oscar Noya and Patarroyo, {Manuel A}",
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On the Evolution and Function of Plasmodium vivax Reticulocyte Binding Surface Antigen (pvrbsa). / Camargo-Ayala, Paola Andrea; Garzón-Ospina, Diego; Moreno-Pérez, Darwin Andrés; Ricaurte-Contreras, Laura Alejandra; Noya, Oscar; Patarroyo, Manuel A.

En: Frontiers in Genetics, Vol. 9, 10.09.2018, p. 372.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - On the Evolution and Function of Plasmodium vivax Reticulocyte Binding Surface Antigen (pvrbsa)

AU - Camargo-Ayala, Paola Andrea

AU - Garzón-Ospina, Diego

AU - Moreno-Pérez, Darwin Andrés

AU - Ricaurte-Contreras, Laura Alejandra

AU - Noya, Oscar

AU - Patarroyo, Manuel A

PY - 2018/9/10

Y1 - 2018/9/10

N2 - The RBSA protein is encoded by a gene described in Plasmodium species having tropism for reticulocytes. Since this protein is antigenic in natural infections and can bind to target cells, it has been proposed as a potential candidate for an anti-Plasmodium vivax vaccine. However, genetic diversity (a challenge which must be overcome for ensuring fully effective vaccine design) has not been described at this locus. Likewise, the minimum regions mediating specific parasite-host interaction have not been determined. This is why the rbsa gene's evolutionary history is being here described, as well as the P. vivax rbsa (pvrbsa) genetic diversity and the specific regions mediating parasite adhesion to reticulocytes. Unlike what has previously been reported, rbsa was also present in several parasite species belonging to the monkey-malaria clade; paralogs were also found in Plasmodium parasites invading reticulocytes. The pvrbsa locus had less diversity than other merozoite surface proteins where natural selection and recombination were the main evolutionary forces involved in causing the observed polymorphism. The N-terminal end (PvRBSA-A) was conserved and under functional constraint; consequently, it was expressed as recombinant protein for binding assays. This protein fragment bound to reticulocytes whilst the C-terminus, included in recombinant PvRBSA-B (which was not under functional constraint), did not. Interestingly, two PvRBSA-A-derived peptides were able to inhibit protein binding to reticulocytes. Specific conserved and functionally important peptides within PvRBSA-A could thus be considered when designing a fully-effective vaccine against P. vivax.

AB - The RBSA protein is encoded by a gene described in Plasmodium species having tropism for reticulocytes. Since this protein is antigenic in natural infections and can bind to target cells, it has been proposed as a potential candidate for an anti-Plasmodium vivax vaccine. However, genetic diversity (a challenge which must be overcome for ensuring fully effective vaccine design) has not been described at this locus. Likewise, the minimum regions mediating specific parasite-host interaction have not been determined. This is why the rbsa gene's evolutionary history is being here described, as well as the P. vivax rbsa (pvrbsa) genetic diversity and the specific regions mediating parasite adhesion to reticulocytes. Unlike what has previously been reported, rbsa was also present in several parasite species belonging to the monkey-malaria clade; paralogs were also found in Plasmodium parasites invading reticulocytes. The pvrbsa locus had less diversity than other merozoite surface proteins where natural selection and recombination were the main evolutionary forces involved in causing the observed polymorphism. The N-terminal end (PvRBSA-A) was conserved and under functional constraint; consequently, it was expressed as recombinant protein for binding assays. This protein fragment bound to reticulocytes whilst the C-terminus, included in recombinant PvRBSA-B (which was not under functional constraint), did not. Interestingly, two PvRBSA-A-derived peptides were able to inhibit protein binding to reticulocytes. Specific conserved and functionally important peptides within PvRBSA-A could thus be considered when designing a fully-effective vaccine against P. vivax.

U2 - 10.3389/fgene.2018.00372

DO - 10.3389/fgene.2018.00372

M3 - Article

C2 - 30250483

VL - 9

SP - 372

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

ER -