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Molecular mechanism explains why P. falciparum only infects humans
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Interactions between a recently-discovered protein specific to the malaria species Plasmodium falciparum, reticulocyte-binding protein homolog 5, and the erythrocyte cell surface receptor, basigin, may explain why this specific malaria strain infects only humans.
P. falciparum-specific reticulocyte-binding protein homolog 5 (RH5) had a significantly lower affinity for chimpanzee basigin (BSG) and did not bind to gorilla BSG at all, according to Beatrice Hahn, MD, of the University of Pennsylvania’s Perelman School of Medicine, and colleagues.
The discovery may provide a molecular explanation for P. falciparum’s specificity to human hosts, the researchers reported in the Proceedings of the National Academy of Science.
“This may also be an important guiding factor in the development of eradication strategies for the elimination of P. falciparum in endemic areas,” Hahn said in a press release from the Wellcome Trust Sanger Institute.
P. falciparum is a member of the Laverania subgenus of parasites, which are known to exhibit strict host specificity.
For example, P. falciparum is specific to humans, whereas other strains such as P. reichenowi, P. billcollinsi and P. gaboni infect only chimpanzees. Other strains, such as P. blacklocki and P. adleri infect only gorillas.
Until recently, obtaining blood samples to study protein interactions between malaria parasites and great ape hosts has been challenging, as both chimpanzees and gorillas are protected species.
But researchers have developed a method to produce these proteins synthetically in laboratories to avoid the use of blood samples from endangered animals, according to study researcher Gavin Wright, MD, of the Wellcome Trust Sanger Institute in the United Kingdom.
“In time, these scientific advances will lead to improved treatments, eradication strategies and, vaccine development for one of the world's major health problems,” Wright said.
“It’s remarkable that the interaction of a single pair of proteins can explain why the most deadly form of malaria is specific to humans,” Julian Rayner, MD, also of the Wellcome Trust Sanger Institute Malaria Program, added. “This research will strengthen eradication strategies by ruling out great apes as possible reservoirs of human infection by P. falciparum.
Disclosure: The study was supported by the Wellcome Trust, Medical Research Council, the University of Pennsylvania Center for AIDS Research Single Genome Amplification Core Facility, and the NIH. The researchers report no relevant financial disclosures.
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