Two domains in alpha interferons influence the efficacy of the antiviral response.

Murine interferon-alpha 1 and murine interferon-alpha 4 share 80% of their amino acids, yet the proteins differ considerably in their ability to protect mouse or hamster cells against viral infection. With the aim of localizing areas within these proteins which influence the biological response we have constructed hybrid alpha 1 alpha 4 genes by means of homologous recombination of the parent genes. When the antiviral activities of these proteins were compared, it appeared that there are at least two domains that affect the biological response to these proteins: area A (amino acids 10-20) and area B (amino acids 55-67). These areas are presumably involved in the interaction between ligand and receptor. Most interestingly, hybrids in which area A from IFN-alpha 1 is combined with area B from alpha 4, have antiviral activities on homologous cells that are one to two orders of magnitude higher than those of the parent proteins.