Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation

S. Dupuis; C. Dargemont; C. Fieschi; N. Thomassin; S. Rosenzweig; J. Harris; S. M. Holland; R. D. Schreiber; J. L. Casanova

doi:10.1126/science.1061154

Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation

S. Dupuis, C. Dargemont, C. Fieschi, N. Thomassin, S. Rosenzweig, J. Harris, S. M. Holland, R. D. Schreiber, J. L. Casanova

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Abstract

Interferons (IFN) α/β and γ induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.

Original language	English
Pages (from-to)	300-303
Number of pages	4
Journal	Science
Volume	293
Issue number	5528
DOIs	https://doi.org/10.1126/science.1061154
State	Published - Jul 13 2001

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title = "Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation",

abstract = "Interferons (IFN) α/β and γ induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.",

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AU - Dupuis, S.

AU - Dargemont, C.

AU - Fieschi, C.

AU - Thomassin, N.

AU - Rosenzweig, S.

AU - Harris, J.

AU - Holland, S. M.

AU - Schreiber, R. D.

AU - Casanova, J. L.

PY - 2001/7/13

Y1 - 2001/7/13

N2 - Interferons (IFN) α/β and γ induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.

AB - Interferons (IFN) α/β and γ induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.

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JO - Science

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Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation

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