A study published in the American Journal of Molecular Neurobiology suggests that infections from the Brazilian Zika lineage may affect communication, growth, and even survival of brain cells. The analyzes found molecular changes caused by the virus that suggest a link to neurological disorders, neurodevelopmental failures, and neurodevelopmental malformations. The work is the result of a partnership between the Neuroproteomics Laboratory of the State University of Campinas (LNP-UNICAMP) with the Institute of Biomedical Sciences of the Federal University of Rio de Janeiro (ICB-UFRJ) and the D’Or Institute for Research and Education (IDOR).
To achieve these results, the study used two types of analysis. “We tested the impact of infections in a 2D model, where cells only divide and stay at an early stage, and in a 3D model that mimics nervous system connections full of signals and stimuli for young cells to transform into neurons. , for example,” explains Giuliana Minardi Nascimento, one of the authors of the article. The biologist emphasizes that the analysis on two models is important for elucidating the relevant aspects of infection at different periods of cell life. “The idea for the study came from precisely these questions: How would cells that are just replicating be affected? Is the process different when they receive a trigger to differentiate and form a nervous system?” Nascimento says.
Each model was divided into groups and infected with one of three strains of the virus: the virus that causes dengue and two varieties of Zika, the African strain and the Brazilian strain. After a period of exposure to viruses, the infected cells underwent a process of separating the proteins present in each sample and testing whether the presence of these organisms could cause changes in activity and cellular composition. “We aim to identify protein changes that always occur when there is a certain infection in these cell types, which we call fingerprinting,” explains Nascimento.
According to Daniel Martins-de-Souza, LNP and study coordinator, the main difference of this work is the analysis of the impact that the Brazilian lineage of the Zika virus can cause on the development of the central nervous system. “Comparison of these three viruses showed us that the effect of the Brazilian Zika virus on nerve cells is so different from the effect caused by the African lineage virus that the profile of cells infected with Dengue fever was more similar to cells exposed to the African Zika virus than to cells exposed to the African Zika virus. exposed to infection. infected with the Brazilian Zika virus,” explains the researcher.
Zika virus infection has been shown to be able to alter the production of proteins important for the formation, survival, and communication of infected cells from the very beginning of their development, which, when transferred to a living system, demonstrates the potential to seriously disrupt the formation of the nervous system. “In the 2D model, we saw that cells infected with the Zika virus understand that something is going to go wrong, stop the cell cycle and no longer reproduce,” explains the researcher. “In addition, DNA damage repair, energy storage and cell arrangement in the brain are also affected. Taken together, these changes show that Zika virus can interfere with the proliferation of immature nerve cells and may even lead to their death.”
The text highlights that these modifications can be critical, especially for fetal development, as when a pregnant woman is infected, Zika virus has the ability to overcome the protective barriers of the uterus and reach the growing fetus, and this characteristic is mainly related to pedigree. Brazilian virus. “If the fetal brain does not develop during infection, and the nerve cells do not proliferate and differentiate correctly, this can lead to malformations of the child’s nervous system,” explains Giuliana Nascimento. The author also says that other neurological diseases, such as Guillain-Barré syndrome, can also be caused by these infections, since they are associated with similar changes in nerve cells.
According to Daniel Martins-de-Souza, these preliminary results may contribute to the understanding, prevention and treatment of these diseases. “In the long term, the proteins and pathways that we describe for the first time could be targets for drugs or even modulations that could prevent microcephaly and other neurological malformations in mothers infected with the Zika virus,” he says. “We put forward a lot of hypotheses, but we need to do some research to prove these hypotheses. We already know a lot about the macroscopic morphology of the microcephalic brain, but we still know little about this Brazilian Zika virus lineage infection and how it can lead to microcephaly,” the researcher concludes.
The text was originally published by Bori’s agency.