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PageLayout: SinglePage PageMode: UseOutlines Language: en Outlines: Item: Title: OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2 Destination: titlink1 Children: Item: Title: Introduction Destination: flink1 Item: Title: Results Destination: flink2 Children: Item: Title: Clinical and epidemiological characteristics of the population under study Destination: slink3 Item: Title: Genetic variants identified in a Spanish cohort of COVID-19 cases Destination: slink4 Item: Title: In silico prediction of structural alterations in a missense variant Destination: slink5 Item: Title: Clinical severity of COVID-19 patients of the Spanish cohort carriers of OAS1 and OAS3 heterozygous missense variants Destination: slink6 Item: Title: Missense variants in the general population Destination: slink7 Item: Title: Genotype of the OAS1 common variant rs10774671 Destination: slink8 Item: Title: Regression analysis Destination: slink9 Item: Title: Effect of OAS1 variants on enzymatic activity Destination: slink10 Item: Title: Effect of OAS1 and OAS3 variants on RNase L activation and viral load Destination: slink11 Item: Title: Effects of loss or gain of function of OAS1 and OAS3 on RNase L activity and viral replication Destination: slink12 Item: Title: Effect of OAS1 and OAS3 on the induction of inflammatory responses Destination: slink13 Item: Title: Inflammatory response of PBMCs to SARS-CoV-2 infection Destination: slink14 Item: Title: OAS3-deficient mice show exacerbated inflammatory responses Destination: slink15 Item: Title: Effect of Oas3 on survival, virus replication, and the induction of innate immune responses in mice Destination: slink16 Item: Title: Discussion Destination: flink17 Children: Item: Title: Limitations of the study Destination: slink18 Item: Title: Resource availability Destination: flink19 Children: Item: Title: Lead contact Destination: slink20 Item: Title: Materials availability Destination: slink21 Item: Title: Data and code availability Destination: slink22 Item: Title: Consortia Destination: flink23 Item: Title: Acknowledgments Destination: flink24 Item: Title: Author contributions Destination: flink25 Item: Title: Declaration of interests Destination: flink26 Item: Title: Supplemental information Destination: falink27 Item: Title: References Destination: blink1 Item: Title: STAR★Methods Destination: flink28 Children: Item: Title: Key resources table Destination: slink29 Item: Title: Experimental model and study participant details Destination: slink30 Children: Item: Title: Human subjects and ethics Destination: tlink1 Item: Title: Animal studies and ethics Destination: tlink2 Item: Title: Method details Destination: slink31 Children: Item: Title: Whole exome sequencing Destination: tlink3 Item: Title: Structural modeling Destination: tlink4 Item: Title: Alignment Destination: tlink5 Item: Title: Selection of variants to analyze their functional effect Destination: tlink6 Item: Title: Determining the phase of multiple OAS variants in the same individual Destination: tlink7 Item: Title: Cell lines Destination: tlink8 Item: Title: Viruses and virus titrations Destination: tlink9 Item: Title: Plasmids Destination: tlink10 Item: Title: Generation of A549 OAS3 KO cells Destination: tlink11 Item: Title: Overexpression of hACE-2 in A549 and HEK293T cells Destination: tlink12 Item: Title: Effect of OAS1 and OAS3 variants on RNA integrity Destination: tlink13 Item: Title: Effect of OAS1 and OAS3 variants on protein expression Destination: tlink14 Item: Title: siRNA-mediated silencing Destination: tlink15 Item: Title: Western blot Destination: tlink16 Item: Title: Effect of OAS1 and OAS3 variants on innate immune responses Destination: tlink17 Item: Title: RT-qPCR Destination: tlink18 Item: Title: Isolation of peripheral blood mononuclear cells (PBMCs) Destination: tlink19 Item: Title: Generation of human recombinant wild type and mutant OAS1 proteins Destination: tlink20 Item: Title: OAS1 enzymatic activity Destination: tlink21 Item: Title: Intratracheal administration of poly(I:C) and sample processing Destination: tlink22 Children: Item: Title: Treatment Destination: ftlink1 Item: Title: Lung RNA extraction Destination: ftlink2 Item: Title: Flow cytometry of the lungs Destination: ftlink3 Item: Title: In vivo assessment of lung protein synthesis Destination: ftlink4 Item: Title: Western blotting Destination: ftlink5 Item: Title: Histological analysis of the lungs Destination: ftlink6 Item: Title: Mouse infection with a mouse-adapted SARS-CoV-2 viral strain Destination: tlink23 Item: Title: Quantification and statistical analysis Destination: slink32 Children: Item: Title: Power analysis for the human studies Destination: tlink24 Item: Title: Regression analysis Destination: tlink25 Item: Title: Analysis pipeline Destination: tlink26 Item: Title: Gene-based association analysis Destination: tlink27 Item: Title: Analysis of rs10774671 Destination: tlink28 Item: Title: Statistical methods for animal studies Destination: tlink29 Info: Title: OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2 Author: Marta L. 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CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: GlyphLessFont Flags: FixedPitch, Symbolic FontBBox: 0, 0, 500, 1000 FontFile2: true XMP: application/pdf doi:10.1016/j.isci.2025.113966 OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2 Marta L. DeDiego Raúl López-Fernández-Sobrino Jordi Pedragosa Darío López-García Aitor Nogales Jordi Durbán Fernando Cardona Laia Llucià-Carol Vanessa Rivero Paula Vazquez-Utrilla Laura Palomo Sanchez-Grande Miriam Cobo Lara Lloret Leonardo Márquez-Kisinousky Francisca Ruiz-Jaén Francisco Lozano Oriol Sibila Rosa Faner Pedro Castro Carlos Domingo Verónica Robles Josep L. Bedini Verónica Rico Daiana Aguero Alex Soriano Andrea Martín Nalda Alba Parra Martínez Roger Colobran Pere Soler-Palacín Alexandre Serra-Llovich Beatriz Dietl M. Jesús Arranz David Dalmau Jaime Signes-Costa Joan Gil-Carbonell José Todolí Jacobo Martínez Silvia Rojo Aida Fiz-López Elisa Arribas Paloma Cal-Sabater David Bernado Marina Vogel Stefan Wiemann Hassan Abolhassani Qiang Pan-Hammarström Aurora Pujol Helen C. Su Danyel Lee Shen-Ying Zhang Jean-Laurent Casanova Israel Fernández-Cadenas Jordi Pérez-Tur Anna M. Planas COVID Human Genetic Effort33 genetics immunology ISCIENCE, 28 (2025) 113966. doi:10.1016/j.isci.2025.113966 The Authors journal ISCIENCE © 2025 The Authors. Published by Elsevier Inc. 2589-0042 28 12 19 December 2025 2025-12-19 113966 113966 10.1016/j.isci.2025.113966 https://doi.org/10.1016/j.isci.2025.113966 2010-04-23 true 10.1016/j.isci.2025.113966 elsevier.com sciencedirect.com VoR 10.1016/j.isci.2025.113966 noindex true 2010-04-23 true PStill version 1.84.42 sciencedirect.com elsevier.com Elsevier 2025-12-01T21:30:10+05:30 2025-12-18T19:18:05+05:30 2025-12-18T19:18:05+05:30 True 1 https://www.elsevier.com/tdm/tdmrep-policy.json PDFlib+PDI 10.0.2p2 (C++/Win64) uuid:92379711-6e19-4af8-9093-e8839ad7b481 uuid:b52dbdbe-2ac1-4b1e-9854-b89a46213e98 http://creativecommons.org/licenses/by-nc-nd/4.0/ Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Contents: Rect: 354, 503, 469, 513 Flags: Print Annotation: Subtype: Link Contents: Rect: 354, 491, 452, 501 Flags: Print Annotation: Subtype: Link Contents: Rect: 354, 479, 470, 489 Flags: Print Annotation: Subtype: Link Contents: Rect: 100, 48, 262, 56 Flags: Print Annotation: 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