Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency

Source: Hits: 37 Pubdate: 2015-04-01

Abstract: Severeinfluenza disease strikes otherwise healthy children and remains unexplained.We report compound heterozygous null mutations in IRF7, which encodes thetranscription factor interferon regulatory factor 7, in an otherwise healthychild who suffered life-threatening influenza during primary infection. Inresponse to influenza virus, the patient’s leukocytes and plasmacytoiddendritic cells produced very little type I and III interferons (IFNs).Moreover, the patient’s dermal fibroblasts and induced pluripotent stem cell(iPSC)-derived pulmonary epithelial cells produced reduced amounts of type IIFN and displayed increased influenza virus replication. These findings suggestthat IRF7-dependent amplification of type I and III IFNs is required forprotection against primary infection by influenza virus in humans. They alsoshow that severe influenza may result from single-gene inborn errors ofimmunity.Abstract: Severeinfluenza disease strikes otherwise healthy children and remains unexplained.We report compound heterozygous null mutations in IRF7, which encodes thetranscription factor interferon regulatory factor 7, in an otherwise healthychild who suffered life-threatening influenza during primary infection. Inresponse to influenza virus, the patient’s leukocytes and plasmacytoiddendritic cells produced very little type I and III interferons (IFNs).Moreover, the patient’s dermal fibroblasts and induced pluripotent stem cell(iPSC)-derived pulmonary epithelial cells produced reduced amounts of type IIFN and displayed increased influenza virus replication. These findings suggestthat IRF7-dependent amplification of type I and III IFNs is required forprotection against primary infection by influenza virus in humans. They alsoshow that severe influenza may result from single-gene inborn errors ofimmunity. 

 


Link: http://www.sciencemag.org/content/early/2015/03/25/science.aaa1578.abstract