Response of IRF7-deficient peripheral blood mononuclear cells to pH1N1 influenza virus infection

IRF7 plays a critical role in the production and amplification of the antiviral type I and III interferon response. Autosomal recessive IRF7-deficiency resulted in life-threatening influenza disease in a 3-year-old child. We studied the impact of IRF7-deficiency in non-hematopoietic tissues (fibroblasts and lung epithelial cells) as well in hematopoietic cells (peripheral blood mononuclear cells (PBMCs)). Genome-wide gene expression analysis demonstrated a profound loss of type I and III IFNs in PBMCs infected with influenza virus. PBMCs were isolated from 4 healthy donors and patients with deficiencies for IRF7 and UNC93B. The cells were infected with influenza virus A/CA/4/2009 at a multiplicity of infection (MOI) of 2 for 8 and 16 hours. Uninfected cells were cultured for 16 hours.