Scientists have worked out how the seasonal flu virus has become resistant to the anti-influenza drug Tamiflu and why these drug-resistant strains have spread explosively in the past two years.
The H1N1 seasonal flu virus first became resistant to Tamiflu more than 10 years ago because of a single genetic mutation. But these strains were unable to spread because the same mutation that conferred resistance to Tamiflu also made the virus less infectious.
However, the researchers have discovered further genetic mutations that overcame this drawback to the drug-resistant strain. These mutations allowed the virus to spread explosively after the 2007-08 flu season so that by the following year, Tamiflu was next to useless against virtually all seasonal H1N1 flu viruses – although still effective against other flu viruses .
Tamiflu works by binding to a chemical called neuraminidase (the "N" in H1N1) that new flu viruses use to escape from an infected human cell. This effectively blocks viral replication and patients feel better.
However, about a decade ago scientists noticed that the H1N1 flu had undergone a mutation called H274Y that allows neuraminidase to work even in the presence of Tamiflu. However, this mutation also interfered with the virus's ability to replicate and to be transmitted, which meant that drug-resistant strains did not spread very far.
However, Jesse Bloom of the California Institute of Technology in Pasadena, California has found two other mutations that appear to overcome the limitation of the drug-resistant strain. Both mutations occurred prior to the H274Y mutation but it is only in the past couple of years that they have come together in the same virus to produce a fully potent, drug-resistant strain.
"We thought it was an interesting evolutionary mystery. Something happened to make the Tamiflu- resistant virus also capable of replicating and spreading like wild-type flu viruses," Dr Bloom said.
"Now, if you've got a second mutation that fixes this problem in H274Y mutants, you'll have a virus that grows very well and is resistant to Tamiflu. That's bad for us, not the virus," he said.
Nobel prize winner David Baltimore, who led the study published in Science, said: "It shows that mutations are not necessarily 'good' or 'bad', but that their effects may depend on the context in which they appear."