RT Journal Article T1 Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation. A1 Hurtado-Guerrero, Isaac A1 Hernaez, Bruno A1 Pinto-Medel, Maria J A1 Calonge, Esther A1 Rodriguez-Bada, Jose L A1 Urbaneja, Patricia A1 Alonso, Ana A1 Mena-Vazquez, Natalia A1 Aliaga, Pablo A1 Issazadeh-Navikas, Shohreh A1 Pavia, Jose A1 Leyva, Laura A1 Alcami, Jose A1 Alcami, Antonio A1 Fernandez, Oscar A1 Oliver-Martos, Begoña K1 IFNAR K1 Immunology K1 Interferon K1 Soluble receptors AB Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß, but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß mediation, and could be a promising treatment against viral infections and immune-mediated diseases. PB MDPI SN 2077-0383 YR 2020 FD 2020-03-31 LK https://hdl.handle.net/10668/26145 UL https://hdl.handle.net/10668/26145 LA en NO Hurtado-Guerrero I, Hernáez B, Pinto-Medel MJ, Calonge E, Rodriguez-Bada JL, Urbaneja P, et al. Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation. J Clin Med. 2020 Mar 31;9(4):959 NO This research was funded by grants from the Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF) “A way to build Europe” research project PI13/00927 and Technological Development Project in health DTS/1800045 to B. Oliver-Martos. Also, this work was partially supported by Instituto de Salud Carlos III and co-funded by European Regional Development Fund (ERDF) “A way to build Europe” (projects RD12/0017/0015 and RD16CIII/0002/0001). EMBO Short-Term Fellowships (7902) and Estancias formativas de investigación, Junta de Andalucía (EF-0169-2018) to I. Hurtado. JL Rodriguez-Bada is supported by grants from Red Temática de Investigación Cooperativa: Red Española de Esclerosis Multiple REEM (RD16/0015/0010). DS RISalud RD Apr 17, 2025