Expression of antiviral activity and induction of 2',5'-oligoadenylate synthetase by conceptus secretory proteins enriched in bovine trophoblast protein-1

Abstract

Establishment of pregnancy in cattle has been proposed to depend on production of a conceptus protein, bovine trophoblast protein-1 (bTP-1), which has a high degree of sequence homology with bovine interferon-α (bIFN-α), especially the alpha II subfamily. A preparation of bovine conceptus secretory proteins enriched for bTP-1 has antiviral and physico-chemical properties similar to other bIFN-α. Antiviral activity is initially detectable in uterine flushings on Day 14 of pregnancy, when the conceptus measures 4-5 mm in length, and increases as the conceptus elongates through Day 18. Day 17 conceptuses produce more than 106 U antiviral activity during 24 h of culture. All IFNs induce the enzyme 2',5'-oligoadenylate synthetase, which catalyzes production of 2',5'-oligo(A), which in turn is involved in antiviral and growth inhibitory effects of IFNs. This enzyme activity is induced in Madin-Darby bovine kidney cells by the partially purified bTP-1 preparation similarly to IFN-α, -β, and γ. LIkewise, the partially purified bTP-1 and bIFN-α(I) induce 2',5'-oligo(A) synthetase activity in monolayers of endometrial epithelial and stromal cells. Compared to epithelial cells, stromal cells have higher baseline activity of 2',5'-oligo(A) synthetase activity (p < 0.01) and show a greater degree of induction in the presence of either the partially purified bTP-1 or bIFN-α(I) (p < 0.01). Also, 2',5'-oligo(A) synthetase of endometrial stromal cells is induced to a greater degree by our enriched bTP-1 preparation than by bIFN-α(I) (p < 0.01). Endometrial 2',5'-oligo(A) synthetase activity increases markedly on Day 18 postestrus in the uterine horn ipsilateral to the CL, lagging by about 1-2 days the dramatic increase in intrauterine antiviral activity. By contrast, endometrial 2',5'-oligo(A) synthetase activity remains low throughout the estrous cycle. These data suggest that the 2',5'-oligo(A) system, which is an important mediator of IFN actions, may be involved in mediating the effect of bTP-1 on uterine function of the cow.