27 January 2023
Severe flu can have genetic links
Published online 22 June 2015
A virus may be responsible for influenza infections, but genetics may also play a role.
An international team of scientists has reported that severe influenza may result from single-gene inborn errors of immunity.
“We provide the first evidence that severe, isolated flu can be genetic,” says Jean-Laurent Casanova, head of St. Giles Laboratory of Human Genetics of Infectious Diseases at Rockefeller University Hospital in New York, USA.
The team, which includes a researcher affiliated with Qatar’s Sidra Medical and Research Center, investigated the case of a seven-year-old girl who suffered life-threatening acute respiratory distress syndrome when infected with pandemic H1N1 2009 influenza A virus when she was 2.5 years old.
They performed whole-exome sequencing, a test that analysed the coding regions of thousands of the girl’s and her parents’ genes. This confirmed that the girl had two mutations in IRF7, a gene that amplifies the production of the antiviral interferon.
White blood cells and plasmacytoid dendritic cells, immune cells that circulate in the blood and are found in peripheral lymphoid organs, were then isolated from the girl’s blood and infected with influenza A virus. They were found to produce very little amounts of type I and type III interferons.
The researchers then took fibroblasts from the girl’s skin and reprogrammed them to become pluripotent stem cells to produce pulmonary epithelial cells. These were also found to produce reduced amounts of type I interferon and increased influenza virus replication in response to infection.
The findings suggest that amplification of interferon types I and III are dependent on IRF7 and required for protection against primary infection by influenza virus.
“What we find is true in this particular patient,” explains Casanova. “It proves that severe flu was not only viral but also genetic. Also, the results have broader significance because they provide proof-of-principle. In medicine, major advances almost always come first with proof-of-principle results,” he says.
Based on the results of this study, the researchers believe that it could be helpful to employ interferon-based strategies to treat life-threatening influenza in children.
Ciancanelli, M. J. et al. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science http://dx.doi.org/10.1126/science.aaa1578 (2015).