Novel interferon delta genes in mammals: cloning of one gene from the sheep, two genes expressed by the horse conceptus and discovery of related sequences in several taxa by genomic database screening.

Abstract: Interferons (IFNs) are cytokines of vertebrates with many biological effects including antiviral, immunoregulatory and antiproliferative activities. Among them, mammalian type I IFNs represents a large family of related proteins, mainly virus-inducible, divided in 10 distinct subfamilies named alpha, beta, omega, delta, epsilon, alphaomega, nu, tau, kappa and zeta (or Limitin). Some type I IFN subfamilies are physiologically expressed by the conceptus during early pregnancy in ungulates. This is the case in ruminants with IFN-tau (which triggers the maintenance of the maternal corpus luteum during early pregnancy) and in the pig with IFN-delta, a type I IFN that was, until now, only described in this species (Lefèvre, F. and Boulay, V., 1993; Lefèvre, F., Guillomot, M., D'Andrea, S., Battegay, S. and La Bonnardière, C., 1998a) and whose biological role in early maternal-fetal interactions is unknown. We present here definitive evidences that IFN-delta is actually more widely represented among mammals. We report the cloning of three genes coding for non-porcine and biologically active IFN-deltas: one from the sheep, named OvIFN-delta, and two from the horse, named EqIFN-delta1 and EqIFN-delta2. Interestingly, OvIFN-delta (139 aa) appears to be the shortest natural type I IFN presently known. Moreover, we identified by genomic database screening nineteen potentially functional IFN-delta genes from various species belonging to the four mammalian lineages (Afrotheria, Xenarthra, Euarchontoglires and Laurasiatheria). These novel type I IFNs display a high rate of identity with previously known porcine IFN-deltas. Phylogenetic analysis indicates that the newly defined IFN-delta family includes murine Limitin/IFN-zeta, their closest neighbor, but is clearly distinct from all other type I families. We also show that, although OvIFN-delta gene transcripts are not detectable in Day-14 and Day-15 sheep conceptuses, the two equine genes are expressed by the horse conceptus tissues at the beginning of pregnancy (Day 16 and Day 22). This suggests that, similar to the pig, IFN-delta could play an important role in maternal-fetal interactions during early pregnancy in the horse.