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

Interferons (IFN) alpha/beta and gamma induce the formation of two transcri ptional activators: gamma-activating factor (CAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mu tation associated with susceptibility to mycobacterial but not viral diseas e. This mutation causes a loss of CAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nucl ear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated b y IFNs. Thus, the antimycobacterial, but not the antiviral, effects of huma n IFNs are principally mediated by GAF.