Characterization of the type I IFN response to virus infection

The type I interferon (IFN) system includes multiple IFN-alpha subtypes, which exhibit considerable identity at the amino acid level. We infer that evolutionary conservation of multiple subtypes has resulted from viral pressures. The inducible IFN gene expression profiles in response to infection with single stranded RNA viruses, sendai and MHV-1 were examined in mouse fibroblast L2 and L929 cells using a quantitative RT-PCR system. Signature profiles of IFN-alpha2, IFN-alpha4 and IFN-alpha5 gene expression were observed in relation to the extent and kinetics of their induction. Promoter region analysis for all the different mouse IFN-alpha genes identified different signature patterns for transcription factor binding sites. Intranasal infection of mice with MHV-1 revealed that susceptible A/J mice mounted a less robust IFN response compared with resistant C57BL/6J mice. In a final series of experiments we provide evidence for the protective effects of IFN-beta against MHV-1 infection in A/J mice.