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Although rabies control has progressed considerably since Louis Pasteur first trialed his vaccine, the disease continues to kill thousands of people who do not have access to treatment. Scientists have traced the evolution of the disease worldwide over different eras in a bid to improve our understanding of and preparedness for emerging infectious diseases.
In 1885, Louis Pasteur successfully conducted the first rabies vaccination on Joseph Meister, a 9-year-old shepherd boy from Alsace. After a century and a half and millions of lives saved, this disease is still rampant in certain Asian and African countries. In a study published on July 17, 2023, in the journal Nature Communications, a team of researchers, including INCEPTION PhD student Andrew Holtz as the lead author, has taken up an audacious challenge: to retrace the evolution of the rabies virus across the world and through the ages, from the late Middle Ages to the present day.
Using computational biology to analyze thousands of DNA sequences
"Scientists can dive into the genomes of viruses to understand where they come from and how they spread. This is no easy task, especially when it comes to ancient diseases that have left us with a lot of incomplete genetic information", begins Andrew Holtz, INCEPTION PhD student researcher in the Institut Pasteur's Lyssavirus Epidemiology and Neuropathology Unit and first author of the study. To this end, the researchers analyzed thousands of DNA sequences from more or less ancient rabies viruses whose origins are known. "The sequences were in some cases incomplete, but we were able to reconstruct them by comparing them with the reference genome, like trying to put together a puzzle from its model," explains Anna Zhukova, a researcher at the Institut Pasteur's Bioinformatics and Biostatistics hub and principal author of the study.
The rapid expansion of rabies from the 14th century onwards
Random mutations and environmental effects have led to slight differences in each sequence analyzed. These differences have enabled researchers to trace the evolutionary and geographical history of rabies. "Our method revealed that the current strain of the virus emerged between 1301 and 1403. By estimating the dates and routes of introduction into each region, we could trace the expansion of rabies worldwide. "We have also highlighted the potential impact of European colonization and the wider role of human beings in the spread of the disease via colonial networks and trade, for example," describes Andrew Holtz.
Understanding the spread of rabies to prevent better and contain it
According to the researchers, this analysis method could improve understanding of how diseases are transmitted and evolve in different geographical areas, opening up new possibilities for saving lives. "By understanding how viruses spread, we can better prepare for and prevent future epidemics. For example, knowledge of the historical transmission patterns of rabies could help develop more precise control strategies. Control is crucial when a virus acts differently in different regions," summarize the researchers. This work also paves the way for similar research on other viruses, using vast quantities of hitherto under-exploited genetic data.
The article is translated from the original prepared by the Departement of Communication and published in the Pasteur Research Journal
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