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

First Author  DeDiego ML Year  2025
Journal  iScience Volume  28
Issue  12 Pages  113966
PubMed ID  41438061 Mgi Jnum  J:380702
Mgi Id  MGI:8273098 Doi  10.1016/j.isci.2025.113966
Citation  DeDiego ML, et al. (2025) OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2. iScience 28(12):113966
abstractText  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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