Relative antiviral activity of in vitro-synthesized murine interferon-alpha 4 and -alpha 1

Murine interferon-alpha 4 (MuIFN-alpha 4) is notable among the MuIFN-alpha subtypes because it lacks 5 amino acids corresponding to positions 103-107 of the other subtypes, yet is the most highly expressed subtype. Site-directed in vitro mutagenesis has been used to modify the genes coding for MuIFN-alpha 4 and MuIFN-alpha 1. The modifications have allowed (i) the in vitro expression of the mature form of each MuIFN-alpha subtype and (ii) the insertion of five amino acids, corresponding to amino acid positions 103-107 of MuIFN-alpha 1, into the MuIFN-alpha 4 sequence. In contrast to previously published data MuIFN-alpha 4 and MuIFN-alpha 1 show only a twofold difference in antiviral activity, with MuIFN-alpha 4 being the more active subtype. In keeping with this observation, it was also found that insertion of the five "missing" amino acids into MuIFN-alpha 4 resulted in an analogue MuIFN-alpha with antiviral activity equivalent to MuIFN-alpha 1. It may be inferred from this work that the deletion of amino acids 103-107 (QVGVQ) is solely responsible for the difference in antiviral activity between MuIFN-alpha 4 and MuIFN-alpha 1.