Expression of Antiviral Activity and Induction of 2′,5′-Oligoadenylate Synthetase by Conceptus Secretory Proteins Enriched in Bovine Trophoblast Protein-11

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 α 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-α1 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-α1 (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-α1 (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 mediathg the effect of bTP-1 on uterine function of the cow.