Single gene cripples flu defence

A report has found that rare mutations in a single gene made one girl genetically susceptible to severe influenza infection.

In 2011, the girl from France, referred to as 'P', was left hospitalised and fighting for her life after contracting flu for the first time at the age of two.

Looking for potential genetic causes, researchers from Rockefeller University sequenced all of the DNA in her genome coding for proteins, as well as that of her parents.

They found that each of P's parents had one working and one faulty copy of the gene IRF7 and P had inherited a mutated copy of the gene from both of them.

IRF7 is responsible for helping to produce a group of proteins called interferons which are released by infected cells to help fight off viral infections. Without a single working copy of the gene, P was left unable to make any working IRF7 protein.

Reporting in Science, the authors tested how P's blood cells responded to infection with viruses in the lab. P's cells failed to produce certain kinds of interferon in response to viral infections, and viruses were able to replicate much faster, which could explain why she was so vulnerable to flu.

By using genetic technologies to add in a working IRF7 gene, the researchers could make her cells act like those from healthy individuals, demonstrating that her lack of a working IRF7 gene was responsible. Similarly, adding artificial interferon protein to her cells prevented viruses from replicating at a higher rate.

Furthermore, blood cells from P's parents produced healthy amounts of interferon when exposed to influenza. 'That really was definitive proof that a single, non-mutated copy of this gene is enough to allow people to mount a response to the virus,' said co-author Dr Michael Ciancanelli.

It appears that P's IRF7 mutations only predispose her towards influenza, and not other viral infections. She has been protected from subsequent bouts of flu by receiving the seasonal vaccination.

'This is the first example of a common, isolated and life-threatening infection of childhood that is shown to be also a genetic disease,' said lead author Professor Jean-Laurent Casanova. He notes that for people like P treatment with medicinal interferon might prevent severe influenza complications.