Loss of the Signature Six Carboxyl Amino Acid Tail from Ovine Interferon-Tau Does Not Affect Biological Activity'

Interferon-tau (IFN-,r) is a type I IFN that is secreted from conceptuses of Bovidae (sheep, cattle, and related ruminant un-gulates) for a few days during early pregnancy. It acts to prolong the life span of the corpus luteum. All secreted forms of IFN-T, like the related IFN-o, are 172 amino acids in length and differ from IFN-ct and- by the presence of six additional amino acids at their carboxyl termini. The aim of this study was to determine whether this carboxyl tail was important for biological activity of IFN-T, particularly for its antiluteolytic function in ewes. Full-length ovine IFN-'r (p3) and a mutated form truncated by six amino acids at its carboxyl terminal (p3Trn6, 166 amino acids) were produced in Escherichia coli. Both proteins had similar antiviral activities (2.12 + 0.92 x 108 IU/mg for p3; 1.96-0.58 x 108 IU/mg for p3Trn6) when tested on Madin-Darby bovine kidney (MDBK) cells. Antiproliferative activity, as mea-sured on human Daudi cells by determining the protein con-centration required to inhibit growth by 50%, was slightly high-er (p < 0.05) for p3Trn6 (7.36- 0.46 pM) than for p3 (13.99 + 0.85 pM). Most importantly, p3 and p3Trn6 were equally ca-pable of prolonging the life span of the corpus luteum of non-pregnant ewes when the proteins were administered at doses of either 60 or 300 tIg/day into the uterine lumen through in-dwelling uterine cannulae from Day 10 to Day 18 postestrus. Therefore, the carboxyl-terminal amino acid extension for IFN-T does not appear to serve a functional role in the action of these proteins