2026-05-29T22:25:11Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/353022026-03-11T07:21:47Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Aliaga-Gaspar, Pablo
author
Brichette Mieg, Isabel
author
Fernández-Arjona, María del Mar
author
Rodríguez-Bada, José Luis
author
Lopez-Moreno, Yolanda
author
Serrano-Castro, Pedro Jesús
author
Fernández Fernández, Oscar
author
Ciano-Petersen, Nicolas Lundahl
author
Oliver-Martos, Begoña
2024-11-25T13:12:21Z
2024-11-25T13:12:21Z
2024
Pablo Aliaga-Gaspar, Isabel Brichette-Mieg, MdM Fernández-Arjona, José Luis Rodríguez-Bada, Yolanda López-Moreno, Pedro Serrano-Castro, Oscar Fernández-Fernández, Nicolás Lundahl Ciano-Petersen, Begoña Oliver-Martos, Recombinant soluble type I interferon receptor exerts antiviral activity by inducing proteins related to autophagy, Biomedicine & Pharmacotherapy, Volume 181, 2024, 117678, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2024.117678.
https://hdl.handle.net/10630/35302
https://doi.org/10.1016/j.biopha.2024.117678
The soluble type I IFN receptor (sIFNAR2) is produced by alternative splicing and is present in body fluids.
Although it can modulate IFN-ß activity, its biological role remains unknown.
Methods: An in-silico study was conducted to compare the structure of recombinant human soluble IFNAR2 (r sIFNAR2) with its native form. The antiviral activity of r-sIFNAR2, produced in BL21-bacteria and CHO cells, was
tested using a cytopathic effect assay including appropriate controls. Viability and toxicity were assessed by MTT
assays. Proteomic analysis using mass spectrometry was conducted in the A549/EMCV bioassay to elucidate the
mechanism of action, and then it was validated by Western blot.
Results: The BL21-sIFNAR2 had a sequence identity of 83.6 % with the native form, showing variations only in
terminal regions. BL21-sIFNAR2 and CHO-sIFNAR2 showed significantly higher percentage of cell viability
compared to the viral control, similar to IFN-ß. Cell viability with BL21-sIFNAR2 was comparable to the cell
control across all tested concentrations.
Proteomic analysis revealed an up regulation of pathways related with autophagy (macroautophagy, autophagy,
pexophagy, and mitophagy) with an SQSTM1 overexpression that was then confirmed by Western Blot, espe
cially after virus infection. However, pathways related to interferon signaling, and antiviral mechanisms
mediated by IFN-stimulated genes were down-regulated.
Conclusion: r-sIFNAR2 exhibits significant antiviral activity regardless of the expression system used for its
production and good safety profile, suggesting its use as a potential antiviral drug. Proteins related to autophagy
are involved in the protection from the virus. This study highlights the biological relevance of soluble cytokine
receptors as effectors so far overlooked
spa
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Farmacología
Medicina
Interferón
Receptores celulares
Recombinant soluble type I interferon receptor exerts antiviral activity by inducing proteins related to autophagy
journal article
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Recombinant soluble type I interferon receptor....pdf