A novel and atypical type one interferon gene expressed by trophoblast during early pregnancy

Low stringency screening of day 14-15 pig conceptus cDNA library using an interferon (IFN)-omega probe has led to the isolation of a novel type one (type I) IFN gene physiologically expressed by trophoblast during the period of implantation in the uterus. It encodes a 170-amino acid preprotein with two potential N-glycosylation sites and a predicted N-terminal signal peptide of 21 residues. This protein was shorter and richer in Cys residues than other type I IFNs and distantly related to all of them including IFN-tau, the trophoblast IFNs of ruminants, with amino acid identities ranging between 27 and 42%. Moreover, its antiviral activity was resistant to neutralization by antisera directed against several IFN-alpha, -beta, -omega, and -tau family members. The pig genome contained only two intronless, non-allelic loci homologous to the cDNA, one of them corresponding to the cDNA. This gene had a single transcription initiation site. Its upstream putative regulatory regions had no similarity with those of other type I IFN genes and did not display the typical clustering of short sequence motifs thought to be involved in virus inducibility but, instead, a modular structure of 30-40-base pair direct repeats. These data highlight the very atypical characteristics of this gene and its product and suggest that it represents the first member of a yet unknown family of type I IFNs present in other mammalian species according to sequence divergence analysis.