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DOI 10.1016/j.isci.2025.113966

Медицинская библиотека · iScience · 2025

OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2.

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, Sanchez-Grande Laura Palomo, 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, Nalda Andrea Martín, Martínez Alba Parra, Colobran Roger, Soler-Palacín Pere, Serra-Llovich Alexandre, Dietl Beatriz, Arranz M Jesús, 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, COVID Human Genetic Effort, Su Helen C, Lee Danyel, Zhang Shen-Ying, Casanova Jean-Laurent, Fernández-Cadenas Israel, Pérez-Tur Jordi, Planas Anna M

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Аннотация

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.

Для цитирования: 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, Sanchez-Grande Laura Palomo, 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, Nalda Andrea Martín, Martínez Alba Parra, Colobran Roger, Soler-Palacín Pere, Serra-Llovich Alexandre, Dietl Beatriz, Arranz M Jesús, 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, COVID Human Genetic Effort, 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. DOI: 10.1016/j.isci.2025.113966.
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