Navigation Links
Tamiflu-resistant influenza: Parsing the genome for the culprits

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 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 genetic mutations 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 genetic code 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 mutations are reason for concern: they could allow the virus 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."


Contact: Lionel Pousaz
Ecole Polytechnique Fdrale de Lausanne

Related biology news :

1. Better preparedness against Tamiflu-resistant influenza viruses
2. H7N9 influenza: History of similar viruses gives cause for concern
3. Research from CHORI scientists demonstrates first genome methylation in fruit fly
4. Genome-wide association studies mislead on cardiac arrhythmia risk gene
5. In the genome of loblolly pine lies hope for better resistance to a damaging disease
6. Loblolly pine genome is largest ever sequenced
7. Loblolly pines immense genome conquered
8. Newly identified small-RNA pathway defends genome against the enemy within
9. The genome of sesame sheds new lights on oil biosynthesis
10. Scripps Wellderly Genome Resource now available to researchers
11. Pond-dwelling powerhouses genome points to its biofuel potential
Post Your Comments:
(Date:5/20/2016)... MINNEAPOLIS , May 20, 2016  VoiceIt ... technology partnership with VoicePass. By working ... user experience.  Because VoiceIt and VoicePass take slightly ... two engines increases both security and usability. ... expressed excitement about this new partnership. ...
(Date:5/12/2016)... , May 12, 2016 , ... published the overview results from the Q1 wave of ... recent wave was consumers, receptivity to a program where ... with a health insurance company. "We were ... share," says Michael LaColla , CEO of Troubadour ...
(Date:5/3/2016)... Lithuania , May 3, 2016  Neurotechnology, ... released the MegaMatcher Automated Biometric Identification System ... of large-scale multi-biometric projects. MegaMatcher ABIS can process ... accuracy using any combination of fingerprint, face or ... MegaMatcher SDK and MegaMatcher Accelerator ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... ... June 23, 2016 , ... Charm ... Mold) microbial test has received AOAC Research Institute approval 061601. , “This is ... last year,” stated Bob Salter, Vice President of Regulatory and Industrial Affairs. “The ...
(Date:6/23/2016)... SAN FRANCISCO , June 23, 2016   ... it has secured $1 million in debt financing from ... to ramp up automation and to advance its drug ... for its new facility. "SVB has been ... goes beyond the services a traditional bank would provide," ...
(Date:6/23/2016)... ... 23, 2016 , ... In a new case report published today in STEM ... who developed lymphedema after being treated for breast cancer benefitted from an injection of ... dealing with this debilitating, frequent side effect of cancer treatment. , Lymphedema ...
Breaking Biology Technology: