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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/228785
OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2
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Recessive deficiency in 2',5' -oligoadenylate synthetase (OAS) or RNase L can cause systemic inflammation in children with SARS-CoV-2 infection, but its role in adult respiratory disease is unclear. We analyzed rare OAS1/OAS3 variants and the common OAS1 rs10774671 polymorphism in 342 COVID-19 patients, assessing enzymatic activity, RNase L activation, viral replication, and inflammation in cell systems and Oas3-deficient mice. Rare heterozygous variants showed impaired RNase L activation but were not enriched in pneumonia cases. In contrast, the rs10774671 A/A genotype (OAS1-p42 isoform) was associated with severe disease (OR = 2.28; 95% CI = 1.13-4.58; p = 0.0107) and reduced viral control despite intact RNase L activation. OAS3 and OAS1-p46 isoform limited viral replication and inflammatory responses, whereas Oas3-deficient mice showed increased cytokines. These findings suggest that common OAS1 variation influences COVID-19 severity, while rare OAS variants may affect inflammation regulation rather than respiratory pathology.
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DEDIEGO, Marta l., LÓPEZ FERNÁNDEZ SOBRINO, Raúl, PEDRAGOSA, Jordi, LÓPEZ GARCÍA, Darío, NOGALES, Aitor, DURBÁN, Jordi, CARDONA, Fernando, LLUCIÀ CAROL, Laia, RIVERO, Vanessa, VAZQUEZ UTRILLA, Paula, PALOMO SANCHEZ GRANDE, Laura, COBO, Miriam, LLORET, Lara, MÁRQUEZ KISINOUSKY, Leonardo, RUIZ JAÉN, Francisca, LOZANO, Francisco, SIBILA, Oriol, FANER, Rosa, CASTRO, Pedro, DOMINGO, Carlos, ROBLES, Verónica, BEDINI, Josep l., RICO, Verónica, AGUERO, Daiana, SORIANO, Alex, MARTÍN NALDA, Andrea, PARRA MARTÍNEZ, Alba, COLOBRAN, Roger, SOLER PALACÍN, Pere, SERRA LLOVICH, Alexandre, DIETL, Beatriz, JESÚS ARRANZ, M., DALMAU, David, SIGNES COSTA, Jaime, GIL CARBONELL, Joan, TODOLÍ, José, MARTÍNEZ, Jacobo, ROJO, Silvia, FIZ LÓPEZ, Aida, ARRIBAS, Elisa, CAL SABATER, Paloma, BERNADO, David, VOGEL, Marina, WIEMANN, Stefan, ABOLHASSANI, Hassan, PAN-HAMMARSTRÖM, Qiang, PUJOL, Aurora, SU, Helen c., LEE, Danyel, ZHANG, Shen ying, CASANOVA, Jean laurent, FERNÁNDEZ CADENAS, Israel, PÉREZ TUR, Jordi, PLANAS, Anna m.. OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2. _iScience_. 2025. Vol. 28, núm. 12, pàgs. 113966. [consulta: 2 de maig de 2026]. [Disponible a: https://hdl.handle.net/2445/228785]