Detalle de: OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2
| Title | OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2 |
| Abstract |
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. |
| Apa Reference | DeDiego, M.L., López-Fernández-Sobrino, R., Pedragosa, J., López-García, D., Nogales, A., Durbán, J., Cardona, F., Llucià-Carol, L., Rivero, V., Vazquez-Utrilla, P., Sanchez-Grande, L.P., Cobo, M., Lloret, L., Márquez-Kisinousky, L., Ruiz-Jaén, F., Lozano, F., Sibila, O., Faner, R., Castro, P., Domingo, C., Robles, V., Bedini, J.L., Rico, V., Aguero, D., Soriano, A., Nalda, A.M., Martínez, A.P., Colobran, R., Soler-Palacín, P., Serra-Llovich, A., Dietl, B., Arranz, M.J., Dalmau, D., Signes-Costa, J., Gil-Carbonell, J., Todolí, J., Martínez, J., Rojo, S., Fiz-López, A., Arribas, E., Cal-Sabater, P., Bernado, D., Vogel, M., Wiemann, S., Abolhassani, H., Pan-Hammarström, Q., Pujol, A., Su, H.C., Lee, D., Zhang, S., Casanova, J., Fernández-Cadenas, I., Pérez-Tur, J. & Planas, A.M. (2025). OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2. iScience, 28(12), 113966. 10.1016/j.isci.2025.113966 |
| Doi | 10.1016/j.isci.2025.113966 |
| Publication Date | Dec 2025 |
| Publication Type | Article |
| Researcher | Lara Lloret Iglesias |
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