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Multifaceted activities of type I interferon are revealed by a receptor antagonist.
Levin, Doron; Schneider, William M; Hoffmann, Hans-Heinrich; Yarden, Ganit; Busetto, Alberto Giovanni; Manor, Ohad; Sharma, Nanaocha; Rice, Charles M; Schreiber, Gideon.
Afiliación
  • Levin D; Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Schneider WM; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
  • Hoffmann HH; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
  • Yarden G; Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Busetto AG; Automatic Control Laboratory, ETH Zurich, 8092 Zurich, Switzerland.
  • Manor O; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Sharma N; Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
  • Rice CM; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
  • Schreiber G; Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. gideon.schreiber@weizmann.ac.il.
Sci Signal ; 7(327): ra50, 2014 May 27.
Article en En | MEDLINE | ID: mdl-24866020
Type I interferons (IFNs), including various IFN-α isoforms and IFN-ß, are a family of homologous, multifunctional cytokines. IFNs activate different cellular responses by binding to a common receptor that consists of two subunits, IFNAR1 and IFNAR2. In addition to stimulating antiviral responses, they also inhibit cell proliferation and modulate other immune responses. We characterized various IFNs, including a mutant IFN-α2 (IFN-1ant) that bound tightly to IFNAR2 but had markedly reduced binding to IFNAR1. Whereas IFN-1ant stimulated antiviral activity in a range of cell lines, it failed to elicit immunomodulatory and antiproliferative activities. The antiviral activities of the various IFNs tested depended on a set of IFN-sensitive genes (the "robust" genes) that were controlled by canonical IFN response elements and responded at low concentrations of IFNs. Conversely, these elements were not found in the promoters of genes required for the antiproliferative responses of IFNs (the "tunable" genes). The extent of expression of tunable genes was cell type-specific and correlated with the magnitude of the antiproliferative effects of the various IFNs. Although IFN-1ant induced the expression of robust genes similarly in five different cell lines, its antiviral activity was virus- and cell type-specific. Our findings suggest that IFN-1ant may be a therapeutic candidate for the treatment of specific viral infections without inducing the immunomodulatory and antiproliferative functions of wild-type IFN.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virosis / Interferón Tipo I / Regulación de la Expresión Génica / Receptor de Interferón alfa y beta Límite: Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virosis / Interferón Tipo I / Regulación de la Expresión Génica / Receptor de Interferón alfa y beta Límite: Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos