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

Interferon (IFN)-alpha from the human placenta was cloned and expressed wit h the aim to study the antiviral, antiproliferative, and immunostimulatory activities. In the present study, we describe three previously unknown sequ ence 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 a ntiviral and antiproliferative potential. The second variant with a Glu32Ty r substitution also displayed diminished antiviral and antiproliferative pr operties, but to a lesser extent than the first clone. For the third varian t, a Ser25Pro substitution in the N-terminal part of the protein and two su bstitutions in the C-terminal part of the protein, Arg126Gly and Ala140Gly, resulted in diminished antiviral but not antiproliferative properties. Reg ardless of the altered antiviral and antiproliferative properties, all sequ ence variants demonstrated natural killer (NK) cell stimulatory potentials paralleling that of prototype IFN-alpha 13. Further studies are needed to g ain a better understanding of the functional significance of different IFN- alpha subtypes at the maternal-fetal interface, in particular in light of t he controversial role the NK cells play in the positive outcome of pregnanc y. (C) 2001 Harcourt Publishers Ltd.