{"doi":"10.30802/aalas-cm-24-058","title":"Studies of C57BL/6J Mice Deficient in Receptors for IFNα/β and IFNγ as a Model for EV-D68 Acute Flaccid Myelitis","abstract":"Enterovirus D68 (EV-D68) causes severe respiratory disease and is a strong candidate as the etiologic agent of acute flaccid myelitis. Acute flaccid myelitis is a rare neurologic disorder that typically affects adolescents less than 13 y old, manifesting as muscle paralysis or weakness. No approved antiviral compounds or vaccines exist for EV-D68. An appropriate mouse model is needed to develop therapeutics. We previously showed that the AG129 mouse strain, which has a double knockout of Ifnar1 and Ifngr1 on the 129/Sv genetic background, exhibits clear clinical signs when infected intraperitoneally with EV-D68 at postnatal day 10. The AGB6 strain, which has the same double knockout, but on the C57BL/6 (B6) genetic background, is more sensitive to dengue virus infections relative to AG129. Given the widespread use of the B6 background in mouse research, we systematically assessed EV-D68 infection in AGB6, the AB6 and GB6 strains, which have single knockouts in Ifnar1 and Ifngr1 , respectively, and the parental B6 strain. AGB6 was highly susceptible to EV-D68, equivalent to AG129. No differences in susceptibility were observed between AGB6 and AB6 and GB6 and B6, suggesting that the IFNγ receptor contributes little to EV-D68 protection. Because B6 is the genetic background for many genetically modified mice, AGB6 facilitates the evaluation of the role of host genes in EV-D68 pathogenesis through genetic crosses. We introduced the knockout allele of Setd3 , a gene essential for enterovirus RNA replication, into AGB6. While EV-D68 lethality was completely penetrant in AGB6- Setd3 +/+ and AGB6- Setd3 +/− mice, all AGB6- Setd3 −/− littermates survived until the experimental endpoint. We conclude that AGB6 is well suited for testing EV-D68 therapeutics. Our study further underscores the importance of SETD3 being a promising therapeutic target for controlling EV-D68 and other enterovirus infections.","journal":"Comparative Medicine","year":2024,"id":482284,"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":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1317987,"name":"Wenqi Song","orcid":"0000-0002-2660-8992","position":1,"is_corresponding":false},{"id":109143,"name":"Jeffrey S. Glenn","orcid":"0000-0002-1843-9965","position":2,"is_corresponding":false},{"id":441323,"name":"Yaw Shin Ooi","orcid":"0000-0001-9014-1365","position":3,"is_corresponding":false},{"id":227957,"name":"Jan E. Carette","orcid":"0000-0002-5187-8070","position":4,"is_corresponding":false},{"id":390452,"name":"Claude M. Nagamine","orcid":"0000-0003-0392-4383","position":5,"is_corresponding":false},{"id":1318321,"name":"Tanya Watarastaporn","orcid":null,"position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:07:14.349221Z","pmid":null,"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":[]}