Exploration of genetic diversity of Plasmodium vivax circumsporozoite protein (Pvcsp) and Plasmodium vivax sexual stage antigen (Pvs25) among North Indian isolates

Abstract

Background Malaria is one of the important vector-borne diseases with high fatality rates in tropical countries. The pattern of emergence and spread of novel antigenic variants, leading to escape of vaccine-induced immunity might be factors responsible for severe malaria. A high level of polymorphism has been reported among malarial antigens which are under selection pressure imposed by host immunity. There are limited reports available on comparative stage-specific genetic diversity among Plasmodium vivax candidate genes in complicated vivax malaria. The present study was planned to study genetic diversity ( Pvcsp and Pvs25 ) among complicated and uncomplicated P. vivax isolates. Methods Pvcsp and Pvs2 -specific PCRs and DNA sequencing were performed on P. vivax PCR positive samples. Genetic diversity was analysed using appropriate software. Results The present study was carried out on 143 P. vivax clinical isolates, collected from Postgraduate Institute of Medical Education and Research, Chandigarh. Among the classic and variant types of Pvcsp , the VK210 (99%; 115/116) was found to be predominant in both complicated and uncomplicated group isolates. Out of the various peptide repeat motifs (PRMs) observed, GDRADGQPA (PRM1) and GDRAAGQPA (PRM2) was the most widely distributed among the P. vivax isolates. Whereas among the Pvs25 isolates, 100% of double mutants (E97 Q /I130 T ) in both the complicated (45/45) as well as in the uncomplicated (81/81) group was observed. Conclusion An analysis of genetic variability enables an understanding of the role of genetic variants in severe vivax malaria.

Genetic polymorphism and natural selection of circumsporozoite protein in Myanmar Plasmodium vivax

“…Among the three PvCSP allelic variants, only two allelic variants, VK210 and VK247, were identified in P. vivax isolates from Myanmar analysed in this study. The VK210 was the dominant allele occurring in 83.6% of Myanmar PvCSP population, which is consistent with previous studies reporting that VK210 is the most common allelic variant in the PvCSP populations from Iran, India, China, Brazil, Thailand, Bangladesh, and Azerbaijan [22][23][24][25][26][27][28][29][30]. Meanwhile, VK247 was more prevalent in certain regions of Colombia [31].…”

Genetic Characterization of Plasmodium vivax Isolates from Pakistan Using Circumsporozoite Protein (PvCSP) and Merozoite Surface Protein-1 (PvMSP-1) Genes as Genetic Markers

“…All the isolates collected were composed of similar pre-repeat sequence (KLKQP) region and conserved post-repeat sequence GGNAANK (PRM4). At the end of the sequence the conserved post-repeat sequence is present as a last section in all of the VK210 isolates, consistent with the ndings of aforementioned studies from India, Iran and Sri Lanka [8,14,20]. Another peptide repeat motif GNGAGGQAA (PRM3) was found at lower frequency (0.6%) in the isolates.…”

“…The results of PvCSP uphold the ndings of the previously published results showing that VK210 strain is predominant type with the prevalence rate ranging between 81-100% [9,12,14,36]. There are few malaria endemic areas where VK247 isolates are commonly present [37,38].…”

“…The essential behind the development of genetic diversity found in the PvCSP gene, across various spatial locations, is the number of PRMs. Difference in the amino acid and nucleotide sequences of the Plasmodium antigens due to variations exist in the repeat unit numbers depicted the pressure of natural selection displayed by the host immune system [14,40]. The arrangement of the main PRM1 and PRM2 factors lead to 15 different haplotypes in PvCSP.…”

“…PvCSP comprises of a central repeat domain that varies across Plasmodium species. It has two non-repetitive domains at N-and C-terminals [13,14]. The varying degree of the amount of peptides in the central repeat region reveals three variants of P. vivax namely VK210, VK247, P. vivax-like [15,16].…”