There is no treatment or vaccine for West Nile, Dengue or Zika viruses. These infections caused by flaviviruses, viruses transmitted by mosquitoes, constitute a major public health problem in the world. Understanding their infection strategy would give scientists the information they need to fight infectious diseases. Laurent Chatel-Chaix of the National Institute for Scientific Research (INRS) recently received $700,000 in funding from the Canadian Institutes of Health Research (CIHR) to unravel this mystery.
“There are probably flaviviruses that we don’t even know about. They are spreading due to changes in insect populations caused in part by climate change. There is an urgent need to identify new antiviral targets and treatments. This will require a better understanding at the molecular level,” explains Professor Laurent Chatel-Chaix, who has been studying flaviviruses for almost 10 years.
In Canada, West Nile virus is endemic and causes severe encephalitis and eventual death. In 2018, Quebec’s health ministry reported 201 West Nile virus cases and 15 deaths — a record number for the province. Dengue virus is the most common arthropod-borne viral disease in the world, and Zika virus infection in utero can lead to severe neurodevelopmental abnormalities in newborns, including congenital microcephaly.
Deciphering the viral strategy to develop better treatments
Professor Chatel-Chaix, an expert in molecular virology, is particularly interested in what happens inside the infected cell. He tries to understand how this type of virus disrupts cellular components to its advantage.
“When the flavivirus enters the cell to replicate, it remodels a number of cellular compartments and reprograms the mitochondria for its own purposes or uses them for energy production. Think of it as a thief breaking into your house, turning off all the alarm systems, rearranging your furniture and emptying your fridge,” says Professor Chatel-Chaix.
This strategy buys the virus time until the cell becomes aware of the infiltration. By deciphering this process of diverting intracellular resources, researchers may be able to find broad-spectrum therapeutic targets.
The team is also working on the NS4B protein present in flaviviruses. “This protein plays a critical role in the replication of the virus genome in the cell, but also in the processes of change involving the mitochondria. Better understanding how the protein promotes viral replication will help us understand how drugs currently in clinical trials target NS4B,” says Professor Chatel-Chaix.
Deciphering the molecular mechanisms that regulate the functioning of these viral factories, whether for Zika, dengue or West Nile, could help researchers like Professor Chatel-Chaix find new treatment strategies to reduce the risk of infection in people with these infectious diseases in Canada and elsewhere.
INRS is a university dedicated exclusively to research and graduate training. Since its creation in 1969, INRS has played an active role in the economic, social and cultural development of Quebec and ranks first for the intensity of research in Quebec. INRS is made up of four interdisciplinary research and training centers in Quebec City, Montreal, Laval and Varennes, specializing in strategic sectors: Water Earth Environment, Energy Materials Telecommunications, Urbanization Culture Society and Armand-Frappier Health Biotechnology. The INRS community includes more than 1,500 students, postdoctoral fellows, faculty members and staff.
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