TY - JOUR
T1 - Size polymorphism and low sequence diversity in the locus encoding the Plasmodium vivax rhoptry neck protein 4 (PvRON4) in Colombian isolates
AU - Buitrago, Sindy P.
AU - Garzón-Ospina, Diego
AU - Patarroyo, Manuel A.
N1 - Funding Information:
We would like to thank Jason Garry for translating and reviewing the manuscript. We would also like to thank Johana Barreto Badillo by her technical assistance and Johanna Forero-Rodr?guez and Carlos Fernando Su?rez for their valuable comments and suggestions. MAP would like to especially thank Liliana Andrea C?rdoba for all her love and support during the last couple of years. This work was financed by the Departamento Administrativo de Ciencia, Tecnolog?a e Innovaci?n (COLCIENCIAS) through grant RC # 0309-2013. SPB received financing through COLCIENCIAS cooperation agreement # 0555-2015.
Publisher Copyright:
© 2016 The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2016/10/18
Y1 - 2016/10/18
N2 - 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.
AB - 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.
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U2 - 10.1186/s12936-016-1563-4
DO - 10.1186/s12936-016-1563-4
M3 - Research Article
C2 - 27756311
AN - SCOPUS:84992410774
SN - 1475-2875
VL - 15
SP - 1
EP - 12
JO - Malaria Journal
JF - Malaria Journal
IS - 1
M1 - 501
ER -