Tamiflu-resistant influenza: Parsing the genome for the culprits

March 31, 2014 by Lionel Pousaz, Ecole Polytechnique Federale de Lausanne
Tamiflu-resistant influenza: Parsing the genome for the culprits
Credit: CC Creative Commons / Andrew Wales

It doesn't take long for the flu virus to outsmart Tamiflu. EPFL scientists have developed a tool that reveals the mutations that make the virus resistant, and they have identified new mutations that may render ineffective one of the few treatments currently available on the market.

Tamiflu is one of the few available treatments for those who come down with the flu. But the virus quickly develops ; 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 ' 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 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 , 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 phenomenon, and other mutations."

New resistant mutations are discovered

To begin, the team led by Jensen and his colleague Matthieu Foll cultured ordinary H1N1 virus in the laboratory. Certain groups were subjected to Tamiflu, others not. Every 48 hours – 13 generations – the biologists sequenced the virus' genome to reveal the genetic mutations that had occurred in the interval.

The more the of viruses exposed to Tamiflu tended to become prevalent with time, the higher the probability that they would confer resistance. With a complex statistics-based software tool, the researchers were able to pinpoint 12 sites on the viral genome that carried suspect variations. One of these was already known, but the rest had not yet been identified.

Weeding out the resistance-conferring mutations

Using their statistical software, the researchers were able to comb through the immensity of the viral and identify only the mutations that were suspected to cause resistance, with a certainty of more than 99% - making their software a powerful tool indeed.

And these newly discovered are reason for concern: they could allow the to be resistant while maintaining an elevated reproductive capacity. Jensen thus doesn't exclude the possibility that pathogenic strains could appear that are both competitive and Tamiflu-resistant, if the mistake of 2008-2009 is repeated. For Foll, first author on the study, "the risk is real, and we need to investigate further."

Explore further: Preparing for Tamiflu-resistant influenza viruses

More information: "Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective," in PLOS Genetics, DOI: 10.1371/journal.pgen.100418

Related Stories

Preparing for Tamiflu-resistant influenza viruses

December 9, 2013
Researchers in Umeå and Uppsala have found that residues of the influenza drug Tamiflu in our environment can make the influenza virus in birds resistant. This can have serious consequences in the event of an influenza pandemic. ...

Resistant flu virus keeps contagiousness

December 10, 2013
A mutant form of the H7N9 flu virus that is resistant to frontline drugs is just as contagious as its non-resistant counterpart, according to a lab test reported on Tuesday.

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.