CONSTITUTIVE AND TROPHOBLAST-SPECIFIC EXPRESSION OF A CLASS OF BOVINE INTERFERON GENES

The early conceptus in sheep and cattle secretes a low molecular weight protein called ovine and bovine trophoblast protein 1 (TP-1) that is critical for establishment of pregnancy. TP-1 is a type I interferon (IFN) and is most related to IFN-omega. Here we have determined if TP-1 genes are regulated similarly to other type I IFNs. Single day 18 bovine conceptuses secrete almost-equal-to 10(5) units of IFN antiviral activity per hour in culture, amounts almost-equal-to 300 times higher than those produced by Sendai virus-induced leukocytes. Although conceptuses express mRNA for IFN-alpha, IFN-omega, and TP-1, TP-1 constitutes > 99% of the IFN produced. In contrast, leukocytes produce predominantly IFN-alpha, although TP-1 mRNA is inducible by Sendai virus to very low levels. TP-1 mRNA is detectable by Northern analysis in conceptuses from early pregnancy but is absent in late gestation placenta and several adult tissues. Transfected bovine TP-1 genes are expressed in human choriocarcinoma (JAR) cells in the absence of any specific stimulus, whereas these cells do not secrete antiviral activity constitutively or after transfection with a bovine IFN-omega gene. The transfected TP-1 gene is not expressed in nontrophoblast cells (mouse L929 and hamster Chinese hamster ovary), however. The 5' promoter region of the TP-1 gene is sufficient to direct trophoblast-specific expression onto a human growth hormone reporter gene in JAR cells. Deletion of the promoter from -450 to -126 results in a 4- to 5-fold decrease in expression. Together these data demonstrate that the genes for TP-1 are inducible by virus but are expressed preferentially in trophoblast cells and are functionally distinct from IFN-omega genes.