Loss of the signature six carboxyl amino acid tail from ovine interferon-tau does not affect biological activity.

Abstract

Interferon-tau (IFN-tau) is a type I IFN that is secreted from conceptuses of Bovidae (sheep, cattle, and related ruminant ungulates) for a few days during early pregnancy. It acts to prolong the life span of the corpus luteum. All secreted forms of IFN-tau, like the related IFN-omega, are 172 amino acids in length and differ from IFN-alpha and -beta 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-tau, particularly for its antiluteolytic function in ewes. Full-length ovine IFN-tau (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 10(8) IU/mg for p3; 1.96 +/- 0.58 x 10(8) IU/mg for p3Trn6) when tested on Madin-Darby bovine kidney (MDBK) cells. Antiproliferative activity, as measured on human Daudi cells by determining the protein concentration required to inhibit growth by 50%, was slightly higher (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 capable of prolonging the life span of the corpus luteum of nonpregnant ewes when the proteins were administered at doses of either 60 or 300 microg/day into the uterine lumen through indwelling uterine cannulae from Day 10 to Day 18 postestrus. Therefore, the carboxyl-terminal amino acid extension for IFN-tau does not appear to serve a functional role in the action of these proteins.