Two extra mutations set the stage for the seasonal influenza virus to evolve into a form that now resists three of the four drugs designed to fight it, researchers reported.
Their study, published in the journal Science, provides a way for scientists to keep an eye out for dangerous mutations in new flu viruses, including the ongoing pandemic of H1N1 swine flu.
Only four drugs are on the market to treat flu and two, the adamantines, are useless against virtually all circulating strains because the viruses have evolved resistance.
Tamiflu, known generically as oseltamivir, is the current drug of choice. It comes as a pill and as an inhaled drug that works in a similar manner called Relenza, or zanamivir generically.
Both can help reduce flu symptoms if taken quickly and can keep the most vulnerable patients out of the hospital, or keep them alive if they are severely ill. But two years ago the common circulating strain of seasonal H1N1 developed resistance to Tamiflu.
How the study was done
Doctors were surprised, because the mutation that help the virus evade the effects of Tamiflu also usually made it a weak virus that did not infect or spread well.
"People have known about this H274Y mutation for over a decade, but the mutation seemed to interfere with the virus's ability to replicate and be transmitted," Jesse Bloom of the California Institute of Technology, who led the study, said in a statement.
"Something happened to make the Tamiflu-resistant virus also capable of replicating and spreading like wild-type flu viruses."
Bloom and Dr David Baltimore, an expert on Aids and on the genetic functions of cells and viruses at Caltech, led a study to find out how this happened.
They found two other mutations in the virus allowed it not only to evade the effects of Tamiflu but to survive and spread.
In addition, the mutations took place before the third and final mutation allowing the virus to evade the drugs. This means that scientists can monitor flu viruses for the initial two mutations to give early warning that they are about to become drug resistant.
What the study revealed
This is important in planning for both seasonal influenza and pandemics. Seasonal flu kills between 250 000 and 500 000 people every year globally.
H1N1 swine flu may have been just slightly more deadly - statistics will take years to gather - but it affects younger adults and children in contrast to seasonal flu, which kills more elderly people.
Currently swine flu is easily treated by Tamiflu but that could change at any time.
So doctors need drugs on hand to save lives and if one drug will be useless, they need to know that because flu must be treated within days of onset for treatment to be useful.
The World Health Organisation said the H1N1 pandemic was not yet over although its most intense activity has passed in many parts of the world. - (Reuters Health, June 2010)