New study uncovers set of parasitic genes associated with persistent malaria infection

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The ability of malarial parasites to persist in the body may be linked to the expression of several clusters of virulence-associated pir genes according to collaborative research from the Francis Crick Institute (London, UK) and the Wellcome Trust Sanger Institute (Cambridge, UK).

All human-infecting Plasmodium species can establish chronic, and often asymptomatic, infections allowing sustained transmission of the parasite. It has previously been reported that the maintenance of this reservoir involves evasion of adaptive immunity by antigenic variation; however, the early events in establishing a long-lasting infection and the genes involved in this have not been well understood.

The study, published recently in Nature Microbiology, aimed to identify which genes are most active in the parasites that establish persistant infection. The team utilized a mouse model to demonstrate that, from an infecting population, only a minority of parasites establish chronic infection and these all express pir genes.

The researchers infected mice with the rodent parasite Plasmodium chabaudi and studied gene expression at different stages of the blood infection. They observed that as few as one in ten of the initial infecting parasites expressed pir genes, however in later stages all persisting Plasmodium expressed this set of genes. The team also confirmed these findings utilizing a second parasite Plasmodium berghei.

Author Jean Langhorne, from the Francis Crick Institute, explained: “We found that the first malaria parasites to appear in the blood were a highly varied population. From this population only a minority of parasites expressing a specific set of pir genes survived to establish a long-lasting, persistent infection. Surprisingly, parasites expressing these pir genes take over as the dominant parasites very quickly, and independently of the mouse’s antibody or T-cell response.”

The findings presented by this study are the first to report a potential role for these pir genes in establishing chronic infection. All species of human-infecting malaria possess related pir genes and the team suggest that a better understanding of these could make it possible to target the parasitic reservoir, and prevent this source of disease transmission.

Co-first author, Adam Reid, from the Sanger Institute, commented: “The pir genes are likely to be common to all species of malaria, and so it is possible that there is a shared mechanism across malaria species that enables them to create chronic infections. The parasite then has a way to establish a reservoir to ensure it is eventually passed on to another human or animal host.”

Langhorne added: “Understanding how certain parasites go on to establish chronic infection and determining how a particular set of pir genes are involved may provide us with a means to prevent chronic infection which could be applicable to all types of malaria in humans.”

Source: Brugat T, Reid AJ, Lin J et al. Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection, Nat. Microbiol. doi:10.1038/nmicrobiol.2016.276 (2017) (Epub ahead of print) www.sanger.ac.uk/news/view/genes-linked-malaria-parasites-ability-persist-body

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