Researchers have pinpointed a rare genetic variation responsible for severe cases of flu in otherwise healthy people, leading to hopes of a new form of antiviral drug.
By studying the 2009 swine flu outbreak, researchers identified a key gene that protects against infection in most people. A less active variant of the gene explains why a small percentage of swine flu sufferers came down with a more severe form of the virus.
Presenting at the British Science Festival, Professor Paul Kellam of the Wellcome Trust Sanger Institute explained that having the variant, called rs12252, of the gene carries a “four to five-fold increased chance of developing severe influenza” from a virus with mild effects in the general population. This means that the one in a thousand people in the UK who carry rs12252 are more likely to suffer complications from the winter flu virus, and may require hospital treatment. Tests on mice with deactivated versions of the gene found that they also suffered more severe flu symptoms when infected.
Discovering the key role of this gene, called IFITM3, in preventing flu infection represents a major breakthrough in the treatment of viral disease. When the gene is activated inside a cell, it makes the cell wall more rigid, preventing viruses from entering and infecting the cell. An antidote to the misery of flu may actually have been hiding inside the human body all along. Drugs that increase the activity of the IFITM3 gene are likely to be effective treatments for other viral diseases too, including Dengue Fever, Yellow Fever or even Ebola.
What is the likelihood of being able to develop this kind of drug? There are strong grounds for optimism, according to Professor Kellam. Variations in this gene do not seem to impair the general health of either humans or animals, and so far no ill effects have been observed from increasing the activity of the gene. Research has discovered a clear link between the activity of the gene and severity of flu infections, so it ticks all of the boxes for a possible gene-based treatment. Similar drugs targeting specific genes have been successfully developed in the past, including antiretroviral treatments such as Maraviroc for HIV.
Could a drug based on the IFITM3 gene be an antibiotic equivalent for viral infections? “We’d like to think it would be”, said Professor Kellam. Such treatments are several years away, but in the mean time identifying at-risk individuals could be a lifeline for health professionals burdened by the demands of the winter flu season. Testing for the rs12252 gene variant can be done rapidly, and could enable early identification of flu patients at increased risk of complications. Antiviral treatments such as Tamiflu, or vaccination, could be then offered to rs12252 carriers, reducing the likelihood of hospitalization and easing pressure on beds and staff.
Dr Jo Barstow is a British Science Association Media Fellow and researcher at the University of Oxford. She was placed with The Conversation, funded by STFC.