{"doi":"10.1101/gad.352725.125","title":"Condensation of human OAS proteins initiates diverse antiviral activities in response to West Nile virus","abstract":"Oligoadenylate synthetases (OASs) are ancient proteins that play a critical role in combatting viruses in mammals. OASs are known to antagonize viral replication by binding viral dsRNA and synthesizing 2'-5'-oligo(A), which activates the antiviral endoribonuclease RNase L. Here, we investigate the antiviral activities of the human OAS isoforms (OAS1, OAS2, OAS3, and OASL) during West Nile virus (WNV) infection. We show that OAS3 is the primary OAS isoform required for activating RNase L. OAS3 condensation on dsRNA proximal to WNV replication organelles initiates RNase L activation. OAS3 contains three distinct dsRNA-binding domains that enhance its condensation on dsRNA. The potential for OAS3 to condense on dsRNA is modulated by dsRNA loads and OAS3 expression level, which can be constitutively expressed or induced by type I interferons. OAS1 and OAS2 do not frequently activate RNase L due to their weak potential to condense on dsRNA. However, they assemble into higher-order structures that aggregate full-length ssRNA viral genomes. OASL does not condense on dsRNA. Instead, OASL localizes to processing bodies, stress granules, and RNase L-induced bodies containing host and viral mRNA. These findings define the process of RNase L activation and elucidate the diversity of substrates and functions of human OAS proteins.","journal":"Genes & Development","year":2025,"id":558364,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1167512,"name":"Ebba K. Blomqvist","orcid":"0009-0001-4386-6440","position":1,"is_corresponding":false},{"id":1459239,"name":"A Cuéllar","orcid":null,"position":2,"is_corresponding":false},{"id":1458797,"name":"Diego Correa","orcid":"0000-0002-9004-4300","position":3,"is_corresponding":false},{"id":549968,"name":"James M. Burke","orcid":"0000-0002-5525-3641","position":4,"is_corresponding":false},{"id":1384129,"name":"Skyler Briggs","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:25.969263Z","pmid":"40588419","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}