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

The type I interferons - interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta) - 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-alpha subtypes are encoded by 12 genes in the mouse [8] whereas IFN-beta is encoded by only one gene [9]. IFN-alpha and IFN-beta 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-alpha and IFN-beta, we have generated a mouse strain with an inactivated IFN-beta gene. We report here that embryonic fibroblasts from such mice produce neither IFN-beta nor IFN-alpha upon Sendai virus infection, whereas the production of IFN-alpha by leukocytes from the same strain of mice is intact, IFN-alpha production in embryonic fibroblasts from IFN-beta(-/-) mice could be rescued by 'priming' the cells using exogenous IFN-beta. These results imply a unique role for IFN-beta in the induction of type I interferons in peripheral tissues. (C) Current Biology Ltd.