Thursday, April 2, 2015

Mutation in human interferon regulatory factor-7 (IRF7) predisposes to severe flu infection

Many times, unexpected reactions to infections (as in severe influenza) or innocuous agents (as in allergy) are based on unsuspected mutations in proteins relevant in immune regulation

The authors showed that the patient inherited one mutated copy of IRF7 from each parent. Functionally, the patient's derived IRF7 lacked the ability to induce IFN-α in a reporter assay (parents were heterozygous and had normal IRF7 functions).

In ex vivo experiments the authors showed that patient's derived plasmacytoid dendritic cells (IFN-producing cells) did not respond to H1N1 infection by up-regulating IFN-α system (though small amount of IFN-β was produced).

Furthermore, the authors showed that the patient's derived fibroblast were highly susceptible in a viral replication assay compared to control fibroblast samples, suggesting that high viral titre in this patient could have produced clinical signs of severe flu.

In summary, this short and simple study provides molecular basis in understanding the disease outcome. In the future, when every newborn will have their DNA sequenced, the parents will be in a better position to carry out necessary prophylaxis and avoid any complications from infections or allergy.

David Usharauli

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