Plasmodium vivax circumsporozoite genotypes: a limited variation or new subspecies with major biological consequences?

Abstract

BackgroundPlasmodium vivax circumsporozoite variants have been identified in several geographical areas. The real implication of the genetic variation in this region of the P. vivax genome has been questioned for a long time. Although previous studies have observed significant association between VK210 and the Duffy blood group, we present here that evidences of this variation are limited to the CSP central portion.MethodsThe phylogenetic analyses were accomplished starting from the amplification of conserved domains of 18 SSU RNAr and Cyt B. The antibodies responses against the CSP peptides, MSP-1, AMA-1 and DBP were detected by ELISA, in plasma samples of individuals infected with two P. vivax CS genotypes: VK210 and P. vivax-like.ResultsThese analyses of the two markers demonstrate high similarity among the P. vivax CS genotypes and surprisingly showed diversity equal to zero between VK210 and P. vivax-like, positioning these CS genotypes in the same clade. A high frequency IgG antibody against the N- and C-terminal regions of the P. vivax CSP was found as compared to the immune response to the R- and V- repetitive regions (p = 0.0005, Fisher's Exact test). This difference was more pronounced when the P. vivax-like variant was present in the infection (p = 0.003, Fisher's Exact test). A high frequency of antibody response against MSP-1 and AMA-1 peptides was observed for all P. vivax CS genotypes in comparison to the same frequency for DBP.ConclusionsThis results target that the differences among the P. vivax CS variants are restrict to the central repeated region of the protein, mostly nucleotide variation with important serological consequences.

Molecular epidemiology of Plasmodium vivax in Latin America: polymorphism and evolutionary relationships of the circumsporozoite gene

“…The better resolution was given by the nucleotide sequence to vk210 a I and a II (detected only in Mexico) and subtype a III (detected only in Nicaragua). As Alu I restriction enzyme digest the whole CRR, it is suggested the presence of other genotypes likely at the CRR of vk210 a [59]. No PCR-RFLP polymorphism was detected in the vk247 isolates.…”

Genotyping of polymorphic marker (MSP3α and MSP3β) genes of Plasmodium vivax field isolates from malaria endemic of Thailand

“…Two types of repetitive domain, VK210 and VK247, are reported in P. vivax isolates distributed worldwide. Owing to this dimorphic of repetitive domain, PvCSP genotypes may not represent markers of intraspecific genetic variations (Souza‐Neiras et al. 2010).…”

Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

“…A possible hypothesis for VK247 higher parasite loads is the “immune selection” occurrence, since the constant VK210 prevalence over all these years in analyzed region may have generated high anti-VK210 antibody titers, hindering the infection establishment by this variant and facilitating by VK247. Even though we did not conduct the antibodies research, it is known that in Brazilian Amazon endemic areas there is a smaller antibody response to VK247 in the presence of VK210 [ 18 ].…”

“…There are still many questions concerning which factors inherent to the host and the parasite are responsible for increased systemic inflammation, parasite load and worsening of the disease. CSP variants infection may affect drug response, symptom severity and humoral response patterns in the host [ 13 , 18 , 19 ], however the influence of these variants in the cytokine response and parasite load remains unclear. Thus, the present study aimed to characterize the molecular variants of CSP and to correlate them with the cytokine profile and the parasite load in studied region.…”