{"id":479378,"date":"2023-06-09T18:45:52","date_gmt":"2023-06-09T21:45:52","guid":{"rendered":"https:\/\/revistapesquisa.fapesp.br\/?p=479378"},"modified":"2023-06-09T18:45:52","modified_gmt":"2023-06-09T21:45:52","slug":"natural-defense-against-chagas","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/natural-defense-against-chagas\/","title":{"rendered":"Natural defense against Chagas"},"content":{"rendered":"

Most individuals from the Arara, Gavi\u00e3o, Karitiana, Suru\u00ed, and eight other Amazonian ethnic groups carry a particular genetic characteristic that seems to protect them from Chagas disease. At least 80% of people in these populations have a subtle alteration in their genome that can reduce the ability of the protozoan Trypanosoma cruzi\u2014<\/em>the single-celled parasite that causes the disease\u2014to invade the body’s cells and cause the disease. This genetic variant, as biologists call it, which is found much more rarely in the inhabitants of other regions around the world, contributed to humankind\u2019s adaptation to the inhospitable environment of the largest rainforest on the planet. Its presence in these populations for thousands of years also offers an additional explanation for an issue yet to be fully understood: the fact that Chagas disease, which affects six million people in Latin America\u2014a third of them in Brazil\u2014is less common among people living in the Amazon.<\/p>\n

A team led by geneticist T\u00e1bita H\u00fcnemeier of the University of S\u00e3o Paulo (USP) identified the high occurrence of this variant\u2014a specific alteration in the vicinity of the PPP3CA gene that lowers its expression\u2014in people from Amazonia after analyzing 600,000 genome excerpts of 118 individuals from 17 ethnic groups native to Brazil, then comparing them with the DNA of populations originating in North America, Asia, Europe, and Africa. The variant is found in at least 80% of people of the native ethnicities in Brazil, but in only 10% of Europeans and 25% of Asians. In Africa, where other diseases caused by protozoa are common, such as malaria and sleeping sickness, the frequency is 59%. The results of the study, published in the journal Science Advances<\/em> in March, also suggest that the mutation became common among groups originating in the Amazon around 7,500 years ago, almost three millennia after humans first arrived in the region.<\/p>\n

\u201cSince the forest is a hostile environment home to a high number of pathogens, we decided to search the genome of native Amazonian peoples for signs that their distant ancestors might have undergone some kind of evolutionary pressure to adapt to the region,\u201d says H\u00fcnemeier. \u201cWe expected to find more genes or genetic alterations that offered protection against viruses or bacteria, but not against protozoa.\u201d<\/p>\n

By analyzing the DNA of the different Brazilian ethnic groups, biologist Kelly Nunes found that the mutation close to PPP3CA showed signs of having undergone natural selection, becoming increasingly common among inhabitants of the region because it favored survival in the environment. The most important of these signs is the fact that among the different ethnic groups from the Amazon, the variant is always accompanied by the same set of genes. It and its neighboring genes form what is known in genetics as a haplotype. \u201cIf this haplotype had not gone through a selection process, you would expect the genes that form it to vary randomly from one population to another,\u201d explains Nunes, who is doing a postdoctorate at H\u00fcnemeier’s laboratory.<\/p>\n

Trypanosoma cruzi<\/em> it is transmitted by the feces of insects commonly known as kissing bugs. When a person scratches themselves, the protozoan penetrates the skin and then invades adjacent cells and spreads around the body through the blood. Inside cells, it multiplies rapidly and within just a few days generates so many copies that it makes the cells explode, releasing more protozoa into the body.<\/p>\n

At Brazilian cardiologist Alexandre Pereira\u2019s laboratory at Harvard University, USA, biologist Gabriela Venturini conducted an experiment to help unravel the role PPP3CA plays in combating Chagas disease. She reduced the amount of protein encoded by the gene in human heart cells (cardiomyocytes) and cultured them with specimens of the parasite. The cells with the lowest amount of protein showed a 25% reduction in the number of protozoa compared to cardiomyocytes with normal protein levels. Although tests have not been carried out using the common variant found in Amazonian Indigenous people, the researchers believe their findings simulate the process that occurs in those individuals.<\/p>\n

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Christophe Simon\u2009\/\u2009Getty Images<\/span><\/a> Woman from the Gavi\u00e3o ethnic group, one of the native peoples of the Amazon who carry a gene variant that can reduce infectionChristophe Simon\u2009\/\u2009Getty Images<\/span><\/p><\/div>\n

Influence in the acute phase<\/strong>
\n\u201cThis experiment helped validate the hypothesis that the gene plays a role in the acute phase of the disease,\u201d explains Pereira, who is also a researcher at USP’s Heart Institute (InCor). This phase occurs within the first few weeks of infection and is often confused with the flu. When the patient is treated at this early stage, the parasite can usually be eliminated. In some cases, however, the protozoan becomes quiescent and can be reactivated if immunity declines. Over decades, the chronic form of the infection can damage organs, including the heart. \u201cThe plan is to repeat the tests with the haplotype found in Amazonian populations and confirm whether it affects the gene’s activity and the parasite’s ability to infect a host,\u201d says Pereira.<\/p>\n

\u201cThe idea is interesting, but the evidence that this gene variant is associated with lower infectivity is still preliminary. It would be interesting to compare the infection capacity of the parasites in cells from individuals with and without the alteration. Another factor is that there are several lineages of the protozoan and species of kissing bug, and not all of them behave in the same way in different environments,\u201d says Sergio Schenkman, a parasitologist from the Federal University of S\u00e3o Paulo (UNIFESP) who specializes in Trypanosoma cruzi<\/em>.<\/p>\n

\u201cThis study is important because it shows an ancient interaction between the parasite and human hosts in a region that many considered free of Chagas disease, but which is rich in insect vectors and wild animals that function as a reservoir for the protozoan,\u201d says biologist Alena Mayo I\u00f1iguez, from the Laboratory of Integrative Parasitology and Paleoparasitology at the Oswaldo Cruz Foundation (FIOCRUZ) in Rio de Janeiro. \u201cThe genetic evidence found by the USP group is consistent with our findings, which suggest that infection by Trypasonoma cruzi <\/em>occurred long before the insect that transmits the parasite adapted to live in human homes,\u201d says the researcher, coauthor of a study that identified infection by the protozoan in human remains at least 4,500 years old found in Minas Gerais.<\/p>\n

Although the results offer a plausible explanation for why there are fewer cases of Chagas in the Amazon than in other regions of the country, the scientists behind the study know that the genetic variant does not explain everything. \u201cThe areas where the disease is endemic are generally situated at the boundaries between urban and nonurban environments, which are less common in the Amazon,\u201d highlights Pereira. There are other factors. Although the parasite exists in the Amazon and many insects there function as a reservoir, the varieties of these vectors are different. \u201cWe do not really know how transmission occurs in the Amazon region,\u201d says Schenkman.<\/p>\n

Projects<\/strong>
\n1.<\/strong> The genomic diversity of Native Americans (n\u00ba 15\/26875-9<\/a>); Grant Mechanism<\/strong> Young Investigator Award; Principal Investigator<\/strong> T\u00e1bita H\u00fcnemeier (USP); Investment<\/strong> R$2,646,774.34.
\n2.<\/strong> Construction of a phage display library for Trypanosoma cruzi<\/em> epitopes to identify an antibody profile in chronic Chagas cardiomyopathy (n\u00ba 19\/11821-1<\/a>); Grant Mechanism<\/strong> Fellowship Abroad; Supervisor<\/strong> Alexandre da Costa Pereira (USP); Beneficiary<\/strong> Gabriela Venturini da Silva; Investment<\/strong> R$267,004.14.<\/p>\n

Scientific article<\/strong>
\nCOUTO-SILVA, C. M. et al<\/em>. Indigenous people from Amazon show genetic signatures of pathogen-driven selection<\/a>. Science Advances<\/strong>. Mar. 8, 2023.<\/p>\n","protected":false},"excerpt":{"rendered":"Genetic alteration capable of protecting people from the disease spread among native peoples of the Amazon 7,500 years ago","protected":false},"author":16,"featured_media":479380,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[159],"tags":[237,247],"coauthors":[105],"class_list":["post-479378","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","tag-genetics","tag-medicine"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/479378","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=479378"}],"version-history":[{"count":2,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/479378\/revisions"}],"predecessor-version":[{"id":481997,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/479378\/revisions\/481997"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media\/479380"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=479378"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=479378"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=479378"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=479378"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}