- Research
PhD student Aïcha Sow identifies a promising viral target for the development of therapies using this model.
Zika virus (ZIKV) infection is a major public health concern, particularly due to the severe brain development defects it can cause in fetuses when pregnant women are infected. One of the most serious outcomes is microcephaly—a condition in which newborns exhibit abnormally small heads. Currently, there are no approved treatments or vaccines for ZIKV, largely because the mechanisms behind the disease remain poorly understood.
Until now, mouse models have been used to study ZIKV infection. However, these models come with significant limitations in terms of number of animals required, technical challenges, high costs, and ethical considerations.
At the Institut national de la recherche scientifique (INRS), Professors Laurent Chatel-Chaix and Kessen Patten combined their expertise in virology and neurodegenerative diseases, respectively, to explore an alternative animal infection model based on zebrafish. This collaboration has led to new insights into how Zika virus affects the developing brain.
Together with Aïcha Sow, a PhD student in virology and immunology, the researchers, who are also Pasteur Network members, developed a zebrafish model that allows them to study ZIKV infection at early developmental stages at the levels of the whole organism, tissues, cells, and molecules.
This research conducted at INRS Armand-Frappier Santé Biotechnologie Research Centre, which constitutes the core Sow’s doctoral thesis, was recently published in PLOS Pathogens. The student is also planning to begin a postdoctoral fellowship at the Institut Pasteur in France in the near future.
A powerful research tool
“Zebrafish is a fascinating model because its anatomical development is very similar to that of humans, but it happens much faster. In just 48 hours, we can observe most organs, including the brain; something that takes several days in mice and months in humans.”
Aïcha Sow, PhD student in virology and immunology
“They are also optically transparent, and fertilization occurs outside the body, which allows us to observe organ development in real time,” she adds.
“It’s an incredible tool for exploring aspects of the disease that we simply cannot study in mice.”
Professor Laurent Chatel-Chaix, Scientific Director of the Containment level 3 laboratory.
The team discovered that Zika virus causes developmental defects in zebrafish larvae similar to those seen in mammals: smaller head size, damage to brain-forming cells, and enlarged brain ventricles. They also identified defects in specific types of neurons and a loss of the stem cells that generate them.
A “key” protein
During her research, Aïcha Sow demonstrated that expressing a single Zika virus protein in zebrafish recapitulates all the effects of infection. This is a major discovery—the first time such a role has been observed for this viral factor in a vertebrate model.
Kessen Patten, who has long used zebrafish to study human diseases, including genetic and neurological disorders.
“Zebrafish are extremely useful in research. They allow us to test many drugs quickly and simultaneously—something we can’t do in humans”
Professor Kessen Patten
Thanks to the transparency and rapid development of zebrafish, researchers can closely observe how the brain forms and how the virus disrupts this process.
The zebrafish model also enables scientists to study the genes involved in the disease and understand the mechanisms at the cellular level. One major advantage: researchers can work with hundreds of larvae at once, leading to more robust and reliable results.
The team hopes this model will open new avenues for understanding the devastating effects of Zika virus on the brain and for testing promising treatments.
About the study
This research was made possible through funding from the Canadian Institutes of Health Research, the Centre of Excellence in Research on Orphan Diseases – Courtois Foundation (CERMO-FC), Brain Canada Foundation (with support from Health Canada and the Azrieli Foundation), and the Fonds de recherche du Québec. Aïcha Sow also received scholarships from the Armand-Frappier Foundation and the Fonds de recherche du Québe
