University of São Paulo: Parasite causing Chagas disease sequesters essential protein in infected cell nucleus

More than a century after being described by science and with about 7 million people currently infected in the world, scientists have achieved important results that can help in the control of Chagas disease. The team led by Professor Munira MA Baqui, from the Department of Cellular and Molecular Biology and Pathogenic Bioagents at the Faculty of Medicine of Ribeirão Preto (FMRP) at USP, discovered that Trypanosoma cruzi , the protozoan that causes the disease, takes control of an essential protein in the nucleus of the infected cell to favor the continuity of its life cycle in the host.

This is the first time, the researchers say, that “evidence of a complex and intimate relationship between T. cruzi and the host cell nucleus during infection has been obtained”. The group observed that the parasite sequesters the U2AF35 protein, essential for the initiation of RNA processing – which directly impacts the host cell’s mature RNAs and their functions.

The invasion and manipulation of the cells of the infected organism is a common strategy of protozoa, but, according to Professor Munira, to date, little is known about what happens in the nucleus and, mainly, about the “regulation of the transcriptional activity of the host cell when infected”. by T. cruzi ”.

The study results were obtained during the doctoral research of Camila Gachet de Castro, under the guidance of Professor Munira, and published by Frontiers in Cellular and Infection Microbiology . The authors made it clear that T. cruzi can alter complex nuclear functions such as modulation of transcription and RNA splicing, a molecule essential for the maintenance of the cell’s biological functions. The professor says that the parasite that causes Chagas disease can “change the expression of proteins that are important for copying information from DNA, decreasing the activity of these proteins and affecting the new ones that would be generated at the end of the process”.

The process involves a complex molecular machinery called a spliceosome, formed by a set of proteins that exist in cells responsible for processing RNA. At the end of the splicing process, there is mature RNA that will be translated into proteins with different functions in the cell.

For the research, the authors studied cells in culture infected with T. cruzi , through cellular, biochemical and molecular biology assays in which they were able to follow the changes that occurred in the nuclear proteins of the infected cells.

Hope for neglected disease control
The USP team’s discovery should be celebrated by the scientific community, as it opens the way for new treatments for a silent and neglected tropical disease. “Existing drugs are few, cause many side effects and do not work in all stages of the disease”, informs the researcher.

In fact, Chagas disease is only curable in the initial phase, which, in general, goes unnoticed and continues to claim victims. According to the World Health Organization (WHO), 30,000 new cases are reported each year of people infected with the parasite.

Discovered in 1909 by the Brazilian public health doctor Carlos Chagas, the disease is endemic in 21 countries on the American continent, with emphasis on Brazil, Argentina, Bolivia, Colombia and Mexico. In Brazil, it is the fourth leading cause of death among parasitic infections, according to data from the Ministry of Health’s special bulletin of April last year.
With the weight of neglect, affecting the poorest regions of the planet, Chagas disease only has curative treatment in its early stages, up to 12 weeks after infection, and it also has the aggravating factor of not showing any symptoms in many people, who only they will discover the disease decades later in a routine exam or when they have more serious involvement, such as the heart.

Given the situation of social vulnerability and lack of drug options, the research findings can “help the discovery of new cellular pathways used by the parasite that were not yet known”, informs Munira, anticipating new and more effective forms of treatment for the disease. . In any case, the professor adds that “more research is needed to discover specific pathways that the parasite uses and to understand its intracellular cycle”.

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