title: Human primary immunodeficiencies of type I interferons.
abstract: Type I interferons (IFN-alpha/beta and related molecules) are essential for protective immunity to experimental infection by numerous viruses in the mouse model. In recent years, human primary immunodeficiencies affecting either the production of (UNC-93B deficiency) or the response to (STAT1 and TYK2 deficiencies) these IFNs have been reported. Affected patients are highly susceptible to certain viruses. Patients with STAT1 or TYK2 deficiency are susceptible to multiple viruses, including herpes simplex virus-1 (HSV-1), whereas UNC-93B-deficient patients present isolated HSV-1 encephalitis. However, these immunological defects are not limited to type I IFN-mediated immunity. Impaired type II IFN (IFN-gamma)-mediated immunity plays no more than a minor role in the pathogenesis of viral diseases in these patients, but the contribution of impaired type III IFN (IFN-lambda)-mediated immunity remains to be determined. These novel inherited disorders strongly suggest that type I IFN-mediated immunity is essential for protection against natural infections caused by several viruses in humans.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale, U550, 75015 Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jouanguy
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sancho-Shimizu
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry; D020022:Genetic Predisposition to Disease; D006564:Herpesviridae / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000821:virology; D026901:Membrane Transport Proteins / Q000378:metabolism; D008954:Models, Biological; D011379:Prognosis; D050794:STAT1 Transcription Factor / Q000378:metabolism; D053634:TYK2 Kinase / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D026901:Membrane Transport Proteins; D050794:STAT1 Transcription Factor; C454130:UNC93B1 protein, human; D053634:TYK2 Kinase