The cysteines in position 1 and 86 of rat interferon-alpha 1 are indispensable for antiviral activity.

The human, bovine, murine and rat interferon (IFN)-alpha families contain 4 conserved cysteines located at positions 1, 29, 99 and 139 that are involved in disulfide bridges. Rat and murine IFN-alpha subspecies carry a fifth Cys (Cys-86) which is not conserved in bovine and human IFN-alpha subspecies except for human IFN-alpha 1. Changing Cys-86 in rat IFN-alpha 1 into Ser or Tyr virtually abolished antiviral activity. As shown by others, the substitution of Cys-86 to Ser in human IFN-alpha 1 had no pronounced effect on activity. This suggests that in contrast to human and bovine IFN-alpha, Cys-86 in rodent IFN-alpha plays a crucial role in receptor binding. Changing Cys-1 to Gly in rat IFN-alpha 1 also destroyed activity, in agreement with results obtained in the human IFN-alpha 1 system.