Scientists zero in on flu virus defences
Flu evolution Scientists have just got a clearer picture of the defences used by a key influenza virus to evade our immune system.
The findings reported today in the journal Science could lead to a new research approach in the holy grail of developing vaccines before new flu viruses evolve.
Influenza A/H3N2 is regarded as a nasty virus that has been infecting humans since 1968.
"Every few years we have a big outbreak of this particular virus," says Australian research team member Dr Ian Barr, deputy director of the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne.
"For example in 2012 we had quite a big influenza season and the majority of that influenza was caused by this type of virus."
In an effort to understand better how flu viruses like this mutate and evade our immune system, Barr and colleagues took a close look at a protein called hemagglutinin (HA), which helps the H3N2 virus bind to cells in our respiratory system.
Our bodies are protected from H3N2 when we develop antibodies to HA, but every few years the protein changes its structure slightly to dodge the immune system.
By substituting amino acids it changes the shape of the molecule as the immune system sees it.
Barr and colleagues looked at the changes that occurred in HA between 1968 and 2003. They found that changes to just seven amino acids of the 566 amino acids that make up HA were responsible for the evolution of a new form of the virus.
"Nine out of 10 of the big changes were due to these seven amino acids," says Barr.
The researchers confirmed their findings by engineering changes to these seven amino acids and testing the antibody response to the new virus in ferrets.
Importantly, the amino acids singled out by Barr and colleagues are close to the site on the HA protein that binds to host cells.
This limits the number of amino acid substitutions that are possible as many changes will alter the protein's structure, interfering with the virus binding process.
"The virus can evolve in a number of different directions," says Barr. "If we can narrow that down to a small number of directions then we've got a better chance of trying to work out which particular virus might be the one which is going to turn up in a year's time."
Ultimately findings such as these could help in the development of vaccines in advance of new forms of virus emerging.
Dr Alan Hampson, chairman of the Influenza Specialist Group, welcomes the research.
"This is great work to find that this is a crucial part of the evolution of the flu virus," he says. "I'm a little surprised that nobody has spotted this in the past."
Hampson says it's a "long bow" to think these findings will directly lead to a vaccine against the next form of influenza, but they do open a research door to scientists trying to predict virus evolution.
He says the research will encourage researchers to make artificial changes to flu viruses at these 7 amino acid sites and to test whether this changes the immune response in laboratory animals.
"Maybe we're starting to see a basis whereby people just may be able to anticipate the sort of changes that could be important," says Hampson. "It gives us a focus on looking for important mutations in the virus."
He says past efforts to outwit the virus turned out to be a dead end and the same may occur with this approach.
"But I guess time alone will tell," says Hampson.