2. Academic Validation
  3. Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway

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

  • Eur J Immunol. 2021 May;51(5):1039-1061. doi: 10.1002/eji.202048793.
Isabelle Meyts 1 2,  Jean-Laurent Casanova 3 4 5 6
Affiliations

Affiliations

  • 1 Department of Immunology, Microbiology and Transplantation, Laboratory of Inborn Errors of Immunity, Leuven, Belgium.
  • 2 Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
  • 3 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
  • 4 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, Paris, France.
  • 5 Imagine Institute, University of Paris, Paris, France.
  • 6 Howard Hughes Medical Institute, New York, NY, USA.
PMID: 33729549 DOI: 10.1002/eji.202048793
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.

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