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Journal Articles European Journal of Immunology Year : 2021

Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway

Abstract

Type I IFNs are so-named because they interfere with viral infection in vertebrate cells. The study of cellular responses to type I IFNs led to the discovery of the JAK-STAT signaling pathway, which also governs the response to other cytokine families. We review here the outcome of viral infections in mice and humans with engineered and inborn deficiencies, respectively, of (i) IFNAR1 or IFNAR2, selectively disrupting responses to type I IFNs, (ii) STAT1, STAT2, and IRF9, also impairing cellular responses to type II (for STAT1) and/or III (for STAT1, STAT2, IRF9) IFNs, and (iii) JAK1 and TYK2, also impairing cellular responses to cytokines other than IFNs. A picture is emerging of greater redundancy of human type I IFNs for protective immunity to viruses in natural conditions than was initially anticipated. Mouse type I IFNs are essential for protection against a broad range of viruses in experimental conditions. These findings suggest that various type I IFN-independent mechanisms of human cell-intrinsic immunity to viruses have yet to be discovered.

Dates and versions

hal-03246535 , version 1 (02-06-2021)

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Isabelle Meyts, Jean‐laurent Casanova. Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway. European Journal of Immunology, 2021, 51 (5), pp.1039-1061. ⟨10.1002/eji.202048793⟩. ⟨hal-03246535⟩
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