EXPRESSION OF INTRACELLULAR INTERFERON CONSTITUTIVELY ACTIVATES ISGF3AND CONFERS RESISTANCE TO EMC VIRAL-INFECTION

The mechanism(s) by which interferon (IFN)-alpha confers resistance to viruses is currently being characterized. Previous studies have shown that binding of IFN-alpha to its high-affinity receptor activates tra nscription factor interferon-stimulated gene factor 3 (ISGF3), which p ositively regulates a number of antiviral genes including 2'-5'-oligoa denylate synthetase (2-5A synthetase), We show that mouse L cells expr essing nonsecreted (intracellular) type I human IFN are less susceptib le to encephalomyocarditis (EMC) virus infection and have increased le vels of 2-5A synthetase, The 2-5A synthetase promoter is constitutivel y induced, and the antiviral effects are most likely mediated through activation of ISGF3, which occurs constitutively in cell lines express ing intracellular interferon, These data suggest that the internalizat ion of IFN-alpha may play a role in the antiviral properties associate d with IFN.