Scientists find gene that can make flu a killer

Sunday, March 25, 2012

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By Kate Kelland

LONDON (Reuters) - A genetic discovery could help explain why flu makes some people seriously ill or kills them, while others seem able to bat it away with little more than a few aches, coughs and sneezes.

In a study published in the journal Nature on Sunday, British and American researchers said they had found for the first time a human gene that influences how people respond to flu infections, making some people more susceptible than others.

The finding helps explain why during the 2009/2010 pandemic of H1N1 or "swine flu", the vast majority of people infected had only mild symptoms, while others - many of them healthy young adults - got seriously ill and died.

In future, the genetic discovery could help doctors screen patients to identify those more likely to be brought down by flu, allowing them to be selected for priority vaccination or preventative treatment during outbreaks, the researchers said.

It could also help develop new vaccines or medicines against potentially more dangerous viruses such as bird flu.

Paul Kellam of Britain's Sanger Institute, who co-led the study and presented the findings in a telephone briefing, said the gene, called ITFITM3, appeared to be a "crucial first line of defense" against flu.

When IFITM3 was present in large quantities, the spread of the virus in lungs was hindered, he explained. But when IFITM3 levels were lower, the virus could replicate and spread more easily, causing more severe symptoms.

People who carried a particular variant of IFTIM3 were far more likely to be taken into hospital when they got flu than people who carried other variants, he added.

"Our research is important for people who have this variant as we predict their immune defenses could be weakened to some virus infections," Kellam said.

"Ultimately as we learn more about the genetics of susceptibility to viruses, then people can take informed precautions, such as vaccination to prevent infection."

MICE EXPERIMENTS HELPED MAKE BREAKTHROUGH

The potential antiviral role of IFITM3 in humans was first suggested in studies conducted by Abraham Brass of the Ragon Institute and Gastrointestinal Unit of Massachusetts General Hospital in the United States. Using genetic screening, he found that it blocked the growth of flu and other viruses in cells.

Teams led by Brass and Kellam then took the work further by knocking out the IFITM3 gene in mice. They found that once these animals contracted flu they had far more severe symptoms than mice with the IFITM3 gene.

In effect, they said, the loss of this single gene in mice can turn a mild case of influenza into a fatal infection.

The researchers then sequenced the IFITM3 genes of 53 patients who had been hospitalized with seasonal or pandemic flu and found that a higher number of them had a particular variant of IFITM3 compared to the general patient population.

The researchers believe this variant results in a shorter version of the protein or one that is less abundant in cells, leaving patients more vulnerable to flu when they get it.

"Our efforts suggest that individuals and populations with less IFITM3 activity may be at increased risk during a pandemic, and that IFITM3 could be vital for defending human populations against other viruses such as avian influenza," said Brass.

(Reporting by Kate Kelland; Editing by Andrew Osborn)

Reuters Health