Interferon-β is required for interferon-α production in mouse fibroblasts

The type I interferons — interferon-a (IFN-a) and interferon-b (IFN-b) — are critical for protection against viruses during the acute stage of viral infection [1,2]. Furthermore, type I interferons have been implicated as important mediators in the regulation of lymphocyte development [3], immune responses [4,5] and the maintenance of immunological memory of cytotoxic T cells [6,7]. The different IFN-a subtypes are encoded by 12 genes in the mouse [8] whereas IFN-b is encoded for by only one gene [9]. IFN-a and IFN-b have a high degree of sequence homology and are thought to interact with the same surface receptor on target cells [10,11]. As an approach to analysing the different biological functions of IFN-a and IFN-b, we have generated a mouse strain with an inactivated IFN-b gene. We report here that embryonic fibroblasts from such mice produce neither IFN-b nor IFN-a upon Sendai virus infection, whereas the production of IFN-a by leukocytes from the same strain of mice is intact. IFN-a production in embryonic fibroblasts from IFN-b–/– mice could be rescued by ‘priming’ the cells using exogenous IFN-b. These results imply a unique role for IFN-b in the induction of type I interferons in peripheral tissues.