The type 1 interferons, and (IFN-/), are comprised act through the IFN-/receptors and STAT1 for the of the products of multiple (up to 12) IFN-genes and induction of IRF-7 in neighboring cells. Upon infection a single IFN-gene. These factors use a common het- with virus, cells expressing IRF-7 are induced to express erodimeric receptor, broadly expressed on most cells. other IFN-genes, ie, non 4 subtypes. This positive The major pathway of intracellular signaling used by feedback for type 1 IFN expression is in effect an IFNIFN-/and their receptors accesses the tyrosine ki-/to IFN-/induction cascade with the virus as a nases, Jak 1 and Tyk 2, activating the signal transducer cofactor. and activators of transcription (STAT) 1 and STAT2 to IL-12 Expression and Function form a STAT1/STAT2 heterodimer. Other pathways, Type 1 IFN can clearly influence the expression and however, are also induced. STAT1/STAT2 complexes function of a variety of cytokines. In contrast to the IFN-associate with a p48 protein, identified as the interferon promotion of IL-12 expression, IFN-/can negatively responsive factor (IRF) 9, to form the interferon-stimu- regulate IL-12 expression. This was first demonstrated lated gene factor-3 (ISGF-3). ISGF-3 induces transcription in the mouse in culture systems using a potent replicaas a result of recognizing interferon stimulated response tion-independent stimulus, fixed staphylococcus aure-