Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Scott Presnell 

PROVIDER: E-GEOD-66486 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Ciancanelli Michael J MJ   Huang Sarah X L SX   Luthra Priya P   Garner Hannah H   Itan Yuval Y   Volpi Stefano S   Lafaille Fabien G FG   Trouillet Céline C   Schmolke Mirco M   Albrecht Randy A RA   Israelsson Elisabeth E   Lim Hye Kyung HK   Casadio Melina M   Hermesh Tamar T   Lorenzo Lazaro L   Leung Lawrence W LW   Pedergnana Vincent V   Boisson Bertrand B   Okada Satoshi S   Picard Capucine C   Ringuier Benedicte B   Troussier Françoise F   Chaussabel Damien D   Abel Laurent L   Pellier Isabelle I   Notarangelo Luigi D LD   García-Sastre Adolfo A   Basler Christopher F CF   Geissmann Frédéric F   Zhang Shen-Ying SY   Snoeck Hans-Willem HW   Casanova Jean-Laurent JL  

Science (New York, N.Y.) 20150326 6233

Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and  ...[more]

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