31 March 2015
New research has shown that a mutation is responsible for susceptibility to severe influenza (flu) virus infections.
Host genetics – human genetic variants that influence susceptibility to infection by pathogens and severity of disease once infected – have long been an area of study. Generally, they do not make a significant difference to the individual, especially not in comparison with alterations in the genome of the pathogens. The flu virus strain that caused the 1918 pandemic, which killed 50 million people world-wide, has been identified as having key mutations that gave it unusual capacity to invade the lungs and cause severe and potentially fatal in otherwise healthy adults, as well as the very old and very young.
However, investigation of a case of severe flu in a young child found that she had mutations in both copies of her IRF7 gene; IRF7 (interferon regulatory factor 7) is a protein involved in the regulation of immune responses to viral infections, notably the production of type I and type III interferons. The patient’s mutations prevented the production of functional IRF7, and hence blocked this important element of her immune response to the influenza infection.
Using lung cells created from the girl’s skin cells, the researchers observed the effects of influenza virus infection and reported that twice as many of these cells were infected at the normal control cells. They therefore propose that IRF7-dependent stimulation of interferon production is a crucial part of effective immune protection against influenza virus infection in humans.
This observation may have therapeutic utility – it is suggested that interferon therapy may be useful in children with severe flu infections. More broadly, it is important for what it reveals about such infections. Senior author Professor Jean-Laurent Casanova of Rockefeller University in New York City told Science: “Severe flu is not only a viral illness, it’s also a genetic illness”.
Of course, the genetics of pathogens, and of human responses to pathogens, are complex, and cases are rarely as clear-cut as this one, or indeed that of rare individuals with the delta32 mutation in the T-cell receptor CCR5 gene who are almost (but not quite) immune to infection by HIV. Whilst interferon responses are important against many viral infections, the patient who suffered severe flu has reportedly not succumbed similarly to other viral infections, suggesting that IRF7 may play a unique and crucial role in influenza infections.