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Tamiflu-resistant influenza: Parsing the genome for the culprits
Date:3/31/2014

Tamiflu is one of the few available treatments for those who come down with the flu. But the virus quickly develops resistance; multiplying at a rate of several generations a day, these tiny pathogens rapidly accumulate genetic mutations. Because of this, they have a good chance of developing counterattacks to the antiviral. How can these infinitesimal variations be identified within the immensity of the virus' genetic code? EPFL researchers have created a computer tool that can shed light on the flu virus' formidable adaptability. They were able to find mutations that conferred resistance that had up to this point not yet been identified. Their software has been made freely available to researchers everywhere, and is the subject of an article published in the journal PLOS Genetics.

Widespread use of Tamiflu leads to resistance

In theory, Tamiflu should only be used by patients in fragile health. But during the 2008-2009 flu season, the drug was used for the first time on a very wide scale. Resistant strains of the virus appeared within just a few weeks. Fortunately, even though the mutation induced a resistance to Tamiflu, it also caused a reduction in the replication rate of the virus. Once the use of the antiviral was dialed back to a more reasonable level, the resistant strains lost their competitive advantage, and they disappeared, submerged by competitors that were sensitive to the drug but had a higher rate of replication.

Resistance always results from random mutations, says Jeffrey Jensen, co-author of the EPFL study. But when a mutation leads to a competitive advantage, for example the ability to resist against a source of aggression, it tends to be passed on to its descendants. "A priori, nothing distinguishes one mutation from another; they're all the result of chance. Our goal is precisely to be able to tell the difference between mutations that make the virus resistant to Tamiflu, thus leading to a selection ph
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Contact: Lionel Pousaz
lionel.pousaz@epfl.ch
41-795-597-161
Ecole Polytechnique Fdrale de Lausanne
Source:Eurekalert

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