Biological characterization of three novel variants of IFN-alpha 13 produced by human placental trophoblast

Abstract

Interferon (IFN)-alpha from the human placenta was cloned and expressed with the aim to study the antiviral, antiproliferative, and immunostimulatory activities. In the present study, we describe three previously unknown sequence variants of IFN-alpha 13 originating from the villous trophoblast. The first variant differed from IFN-alpha 13 by a Cys99Arg substitution and a 10-amino acid C-terminal deletion, which led to a severe reduction of the antiviral and antiproliferative potential. The second variant with a Glu32Tyr substitution also displayed diminished antiviral and antiproliferative properties, but to a lesser extent than the first clone. For the third variant, a Ser25Pro substitution in the N-terminal part of the protein and two substitutions in the C-terminal part of the protein, Arg126Gly and Ala140Gly, resulted in diminished antiviral but not antiproliferative properties. Regardless of the altered antiviral and antiproliferative properties, all sequence variants demonstrated natural killer (NK) cell stimulatory potentials paralleling that of prototype IFN-alpha 13. Further studies are needed to gain a better understanding of the functional significance of different IFN-alpha subtypes at the maternal-fetal interface, in particular in light of the controversial role the NK cells play in the positive outcome of pregnancy.