Size polymorphism and low sequence diversity in the locus encoding the Plasmodium vivax rhoptry neck protein 4 (PvRON4) in Colombian isolates

Background: Designing a vaccine against Plasmodium vivax has focused on selecting antigens involved in invasion mechanisms that must have domains with low polymorphism for avoiding allele-specific immune responses. The rhoptry neck protein 4 (RON4) forms part of the tight junction, which is essential in the invasion of hepatocytes and/or erythrocytes; however, little is known about this locus’ genetic diversity. Methods: DNA sequences from 73 Colombian clinical isolates from pvron4 gene were analysed for characterizing their genetic diversity; pvron4 haplotype number and distribution, as well as the evolutionary forces determining diversity pattern, were assessed by population genetics and molecular evolutionary approaches. Results: ron4 has low genetic diversity in P. vivax at sequence level; however, a variable amount of tandem repeats at the N-terminal region leads to extensive size polymorphism. This region seems to be exposed to the immune system. The central region has a putative esterase/lipase domain which, like the protein’s C-terminal fragment, is highly conserved at intra- and inter-species level. Both regions are under purifying selection. Conclusions: pvron4 is the locus having the lowest genetic diversity described to date for P. vivax. The repeat regions in the N-terminal region could be associated with immune evasion mechanisms while the central region and the C-terminal region seem to be under functional or structural constraint. Bearing such results in mind, the PvRON4 central and/or C-terminal portions represent promising candidates when designing a subunit-based vaccine as they are aimed at avoiding an allele-specific immune response, which might limit vaccine efficacy. © 2016 The Author(s).

• Fecha de publicación: 2016
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/22548
• Acceso en línea: https://doi.org/10.1186/s12936-016-1563-4; https://repository.urosario.edu.co/handle/10336/22548
• Palabra clave: Esterase; Rhoptry neck protein 4; Tight junction protein; Triacylglycerol lipase; Unclassified drug; Protozoal dna; Protozoal protein; Amino terminal sequence; Article; Carboxy terminal sequence; Colombia; Controlled study; Dna sequence; Gene; Genetic conservation; Genetic polymorphism; Genetic variability; Immune system; Nonhuman; Plasmodium vivax; Purifying selection; Pvron4 gene; Tandem repeat; Adolescent; Adult; Chemistry; Cluster analysis; Female; Genetic variation; Genetics; Haplotype; Human; Isolation and purification; Male; Middle aged; Molecular evolution; Parasitology; Phylogeny; Plasmodium vivax; Plasmodium vivax malaria; Sequence homology; Young adult; Adolescent; Adult; Cluster analysis; Colombia; Female; Genetic variation; Haplotypes; Humans; Male; Middle aged; Phylogeny; Plasmodium vivax; Protozoan proteins; Sequence homology; Young adult; Functional restriction; Genetic diversity; Natural selection; Plasmodium vivax; Pvron4; Rhoptry; Tandem repeat; molecular; protozoan; vivax; dna; Dna; Evolution; Malaria; Sequence analysis
• License: Abierto (Texto Completo)