Researchers have found a genetic flaw that may explain why some people get more ill with flu than others. The study was reported in the journal Nature this Sunday, where researchers said the variant of the IFITM3 gene was much more common in people hospitalized for flu than in the general population. It controls a malformed protein, which makes cells more susceptible to viral infection. Experts said those with the flaw could be given the flu jab, like other at-risk groups.
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 Professor Paul Kellam of the Wellcome Trust Sanger Institute, 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.
Professor Paul Kellam who co-led the research, said, “At the moment, if someone is in a more vulnerable group because of co-morbidity [another health problem], they would be offered the flu vaccine. This is the idea here.” But he said having this variant would not make any difference to how people were treated. Prof Kellam added, “Our research is important for people who have this variant as we predict their immune defenses could be weakened to some virus infections. Ultimately as we learn more about the genetics of susceptibility to viruses, then people can take informed precautions, such as vaccination to prevent infection.”
Professor Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London, said, “This new discovery is the first clue from our detailed study of the devastating effects of flu in hospitalized patients. It vindicates our conviction that there is something unusual about these patients.”
Sir Mark Walport, director of the Wellcome Trust, said, “During the recent swine flu pandemic, many people found it remarkable that the same virus could provoke only mild symptoms in most people, while, more rarely, threatening the lives of others. This discovery points to a piece of the explanation: genetic variations affect the way in which different people respond to infection. This important research adds to a growing scientific understanding that genetic factors affect the course of disease in more than one way. Genetic variations in a virus can increase its virulence, but genetic variations in that virus's host - us - matter greatly as well.”
New insights into how IFITM3 protein protects against severe flu