A PARASITE that claims around 50,000 lives a year in Latin America could use an entirely novel mechanism to cause disease. A study of patients with Chagas disease has found segments of the parasite’s DNA integrated into their genomes.
Besides viruses, no other organism that causes disease in animals has been found to integrate its DNA into its host. So not surprisingly, reaction to the new finding has been mixed.
“If integration does happen, it is going to be a very rare event,” says Rick Tarleton at the University of Georgia in Athens, “I think it is highly unlikely to have any relevance to the disease in humans.” Others are more open to the possibility. “I find it amazing, but I don’t doubt it,” says David Engman at Northwestern University in Chicago.
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Chagas disease infects around 17 million people in Latin America, and its range is extending, with cases as far north as Tennessee. The disease, which is caused by the protozoan Trypanosama cruzi, is poorly understood, and there is no effective vaccine.
One particularly puzzling aspect of the disease is its variability. In the initial acute phase, the parasite infects blood cells, causing fever and sometimes swelling of the face and eyes. But it is rarely fatal, and patients often fail to get medical attention. The parasite then goes to ground for 10 or 20 years, during which time it invades most organs. Two-thirds of these chronic sufferers remain unaware that they are infected with the parasite, but the others eventually die from the disease.
How the parasite causes death in the chronic phase is controversial. Some researchers believe that it is the result of accumulated damage to the heart muscles by the parasite. Others believe that an immune reaction directed at the parasite and host’s tissues does the damage.
Whatever the truth, the new finding promises to stir up the debate even further.
Antonio Teixeira and his colleagues at the University of Brasilia in Brazil examined 13 patients with the chronic infection. They detected sequences of 100 to 500 of the parasite’s nucleotides, or DNA building blocks, integrated into the patients’ genomes at one or more locations (Cell, vol 118, p 175). One of the next steps, says Teixeira, will be to investigate whether the integrated parasite DNA is expressed as RNA or protein – one of the most obvious ways it could play a role in causing Chagas.
If the parasite DNA is expressed, that could explain why the disease differs so much between people, as the exact course of the disease could depend on where on the genome the parasite DNA is incorporated.
Meanwhile, the researchers have confirmed the human results by infecting rabbit and chickens with the parasite. The parasite DNA integrated into the genomes of both animals, and the chickens died of Chagas-like symptoms.
The team also detected the parasite DNA in the genomes of chickens two generations on from the birds originally infected. That shows that parasite DNA can be spread via the host genome in chickens, and raises the intriguing possibility that Chagas might also be an inheritable genetic disease in humans. There are no reports of such cases, but, says Engman, that may simply be because no one has looked.