Analysis of Pvama1 genes from China-Myanmar border reveals little regional genetic differentiation of Plasmodium vivax populations

Zhu, Xiaotong; Zhao, Pan; Wang, Si; Liu, Fei; Liu, Jun; Wang, Jian; Zhou, Yang; Yan, Guiyun; Fan, Qi; Cao, Yaming

doi:10.1186/s13071-016-1899-1

Cited by 17 publications

(25 citation statements)

References 69 publications

(102 reference statements)

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“…One of the possible reason for higher immunogenicity for PvMSP-1 19 could be its conserved genetic nature, which were reported in many studies [21, 42–47] and the similar observation were recorded in our field isolates collected from Chennai, Nadiad and Rourkela (unpublished data). In contrast, Pvama - 1 gene found to be highly polymorphic at these three study sites (unpublished data) and also in various previous studies [48–54]. Another possible reason could be higher exposure of PvMSP-1 19 on the surface of infected RBCs until the end of the intracellular cycle [27].…”

Section: Discussionsupporting

confidence: 58%

Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India

Kale

Yadav

Rao

et al. 2019

Malar J

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BackgroundIdentifying highly immunogenic blood stage antigens which can work as target for naturally acquired antibodies in different eco-epidemiological settings is an important step for designing malaria vaccine. Blood stage proteins of Plasmodium vivax, apical membrane antigen-1 (PvAMA-1) and 19 kDa fragment of merozoite surface protein (PvMSP-119) are such promising vaccine candidate antigens. This study determined the naturally-acquired antibody response to PvAMA-1 and PvMSP-119 antigens in individuals living in three geographically diverse malaria endemic regions of India.MethodsA total of 234 blood samples were collected from individuals living in three different eco-epidemiological settings, Chennai, Nadiad, and Rourkela of India. Indirect ELISA was performed to measure human IgG antibodies against recombinant PvAMA-1 and PvMSP-119 antigens. The difference in seroprevalence and factors associated with antibody responses at each site was statistically analysed.ResultsThe overall seroprevalence was 40.6% for PvAMA-1 and 62.4% for PvMSP-119. Seroprevalence to PvAMA-1 was higher in Chennai (47%) followed by Nadiad (46.7%) and Rourkela (27.6%). For PvMSP-119, seroprevalence was higher in Chennai (80.3%) as compared to Nadiad (53.3%) and Rourkela (57.9%). Seroprevalence for both the antigens were found to be higher in Chennai where P. vivax is the dominant malaria species. In addition, heterogeneous antibody response was observed for PvAMA-1 and PvMSP-119 antigens at each of the study sites. Two factors, age and malaria positivity were significantly associated with seropositivity for both the antigens PvAMA-1 and PvMSP-119.ConclusionThese data suggest that natural acquired antibody response is higher for PvMSP-119 antigen as compared to PvAMA-1 antigen in individuals living in three geographically diverse malaria endemic regions in India. PvMSP-119 appears to be highly immunogenic in Indian population and has great potential as a malaria vaccine candidate. The differences in immune response against vaccine candidate antigens in different endemic settings should be taken into account for development of asexual stage based P. vivax malaria vaccine, which in turn can enhance malaria control efforts.

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Section: Discussionsupporting

confidence: 58%

Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India

Kale

Yadav

Rao

et al. 2019

Malar J

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“…Numbered black residues: amino acids with possible influences for DmelOrco VUAA-binding and sensitivity [cysteines, Turner et al 37 ; aspartates 357 and 466 36 , the respective position on DmelOrco related to the B. mori tyrosine 464 38 , for which mutagenization alters current–voltage relationships, and Potassium selectivity (tyrosine 478), and their respective positions on CpomOrco (right)]. Yellow residues: Calmodulin binding sites (“SAIKYWVER” 50 ). Red residues: ICL-3 histidine (left) and the respective substitution on CpomOrco (Q, right).…”

Section: Resultsmentioning

confidence: 99%

Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3

Bobkov

Walker

Cattaneo

2021

Sci Rep

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Amino acid substitutions within the conserved polypeptide sequence of the insect olfactory receptor co-receptor (Orco) have been demonstrated to influence its pharmacological properties. By sequence analysis and phylogenetic investigation, in the Lepidopteran subgroup Ditrysia we identified a fixed substitution in the intracellular loop-3 (ICL-3) of a conserved histidine to glutamine. By means of HEK293 cells as a heterologous system, we functionally expressed Orco from the Ditrysian model Cydia pomonella (CpomOrco) and compared its functional properties with a site-directed mutagenized version where this ICL-3-glutamine was reverted to histidine (CpomOrcoQ417H). The mutagenized CpomOrcoQ417H displayed decreased responsiveness to VUAA1 and reduced response efficacy to an odorant agonist was observed, when co-transfected with the respective OR subunit. Evidence of reduced responsiveness and sensitivity to ligands for the mutagenized Orco suggest the fixed glutamine substitution to be optimized for functionality of the cation channel within Ditrysia. In addition, contrary to the wild type, the mutagenized CpomOrcoQ417H preserved characteristics of VUAA-binding when physiologic conditions turned to acidic. Taken together, our findings provide further evidence of the importance of ICL-3 in forming basic functional properties of insect Orco- and Orco/OR-channels, and suggest involvement of ICL-3 in the potential functional adaptation of Ditrysian Orcos to acidified extra-/intracellular environment.

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“…This observation was further reinforced by the very low F ST value obtained among these GMS populations (F ST = 0.025-0.085). Studies on vaccine candidate genes such as PvAMA1 genes also showed high diversity and little differentiation of the P. vivax parasites from China-Myanmar border [67]. Nevertheless, parasite populations from the GMS did fall into several distinctive clades, suggesting the presence of gene flow barriers or/and divergent selection on the Pvmdr1 protein.…”

Section: Discussionmentioning

confidence: 99%

Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination

et al. 2020

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Background: The malaria elimination plan of the Greater Mekong Subregion (GMS) is jeopardized by the increasing number of Plasmodium vivax infections and emergence of parasite strains with reduced susceptibility to the frontline drug treatment chloroquine/primaquine. This study aimed to determine the evolution of the P. vivax multidrug resistance 1 (Pvmdr1) gene in P. vivax parasites isolated from the China-Myanmar border area during the major phase of elimination. Methods: Clinical isolates were collected from 275 P. vivax patients in 2008, 2012-2013 and 2015 in the China-Myanmar border area and from 55 patients in central China. Comparison was made with parasites from three border regions of Thailand. Results: Overall, genetic diversity of the Pvmdr1 was relatively high in all border regions, and over the seven years in the China-Myanmar border, though slight temporal fluctuation was observed. Single nucleotide polymorphisms previously implicated in reduced chloroquine sensitivity were detected. In particular, M908L approached fixation in the China-Myanmar border area. The Y976F mutation sharply decreased from 18.5% in 2008 to 1.5% in 2012-2013 and disappeared in 2015, whereas F1076L steadily increased from 33.3% in 2008 to 77.8% in 2015. While neutrality tests suggested the action of purifying selection on the pvmdr1 gene, several likelihood-based algorithms detected positive as well as purifying selections operating on specific amino acids including M908L, T958M and F1076L. Fixation and selection of the nonsynonymous mutations are differently distributed across the three border regions and central China. Comparison with the global P. vivax populations clearly indicated clustering of haplotypes according to geographic locations. It is noteworthy that the temperate-zone parasites from central China were completely separated from the parasites from other parts of the GMS. Conclusions: This study showed that P. vivax populations in the China-Myanmar border has experienced major changes in the Pvmdr1 residues proposed to be associated with chloroquine resistance, suggesting that drug selection may play an important role in the evolution of this gene in the parasite populations.

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Analysis of Pvama1 genes from China-Myanmar border reveals little regional genetic differentiation of Plasmodium vivax populations

Cited by 17 publications

References 69 publications

Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India

Antibody responses within two leading Plasmodium vivax vaccine candidate antigens in three geographically diverse malaria-endemic regions of India

Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3

Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination

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