Vivax Malaria and the Potential Role of the Subtelomeric Multigene vir Superfamily

Abstract

Vivax malaria, caused by Plasmodium vivax, remains a public health concern in Central and Southeast Asia and South America, with more than two billion people at risk of infection. Compared to Plasmodium falciparum, P. vivax is considered a benign infection. However, in recent decades, incidences of severe vivax malaria have been confirmed. The P. falciparum erythrocyte membrane protein 1 family encoded by var genes is known as a mediator of severe falciparum malaria by cytoadherence property. Correspondingly, the vir multigene superfamily has been identified as the largest multigene family in P. vivax and is implicated in cytoadherence to endothelial cells and immune response activation. In this review, the functions of vir genes are reviewed in the context of their potential roles in severe vivax malaria.

Genetic diversity and natural selection analysis of VAR2CSA and vir genes: implication for vaccine development

“…There is mounting evidence that Plasmodium VSAs families are not exclusively associated with blood-stage infection but also play a potential role in various mechanisms throughout the parasite’s life cycle, making them suitable targets for vaccine development studies [ 22 , 23 ]. Currently, two gestational malaria vaccine candidates, based on fragments of the VAR2CSA protein from 3D7 and FCR3 reference strains, are in phase Ia/b clinical trials [ 24 ].…”

“…This genetic diversity was accentuated by a large number of insertions and deletions up to 30 nucleotides long. The diversification of these genes is strongly associated with random recombination, particularly facilitated by their sub-telomeric localization [ 23 , 29 ]. In contrast, vir 4 and vir 27 exhibit a higher degree of conservation, with only 1.02% and 2.21% of segregating sites across the gene, respectively.…”

“…Secondly, the biological mechanism of mutually exclusive expression of the 60 var genes in P. falciparum and their implication in pathogenesis is not yet elucidated [ 22 ]. Similarly, only a small number of vir genes have been studied by a limited number of authors so far [ 23 ]. Only 10 vir genes out of > 1200 identified have been studied genomically or immunologically.…”

Plasmodium falciparum CLAG Paralogs All Traffic to the Host Membrane but Knockouts Have Distinct Phenotypes

“…These exported proteins are often encoded by multigene families that facilitate antigenic variation and evasion of host immunity [ 4 , 5 , 6 ]. Notably, members of these families are typically in subtelomeric regions, where active recombination produces new variants that increase diversity [ 7 , 8 ]. Most of these multigene families encode proteins that function in cytoadherence or immune evasion [ 9 ].…”

Special Issue: “Parasitic Infection and Host Immunity”: Editorial

“…Relevant to the topic, Goo, Y. K. et al [11] made a valuable contribution by discussing the biological and pathophysiological aspects of malaria caused by P. vivax from the perspective of the subtelomeric vir multigene superfamily. In P. falciparum, the var gene family encoding PfEMP1 protein plays a key role in antigenic variation and cytoadherence [12].…”