{"doi":"10.1172/jci188495","title":"Immune cells promote paralytic disease in mice infected with enterovirus D68","abstract":"Enterovirus D68 (EV-D68) is associated with acute flaccid myelitis (AFM), a poliomyelitis-like illness causing paralysis in young children. However, the mechanisms of paralysis are unclear, and antiviral therapies are lacking. To better understand EV-D68 disease, we inoculated newborn mice intracranially to assess viral tropism, virulence, and immune responses. WT mice inoculated intracranially with a neurovirulent strain of EV-D68 showed infection of spinal cord neurons and developed paralysis. Spinal tissue from infected mice revealed increased levels of chemokines, inflammatory monocytes, macrophages, and T cells relative to those in controls, suggesting that immune cell infiltration influences pathogenesis. To define the contribution of cytokine-mediated immune cell recruitment to disease, we inoculated mice lacking CCR2, a receptor for several EV-D68-upregulated cytokines, or RAG1, which is required for lymphocyte maturation. WT, Ccr2-/-, and Rag1-/- mice had comparable viral titers in spinal tissue. However, Ccr2-/- and Rag1-/- mice were significantly less likely to be paralyzed relative to WT mice. Consistent with impaired T cell recruitment to sites of infection in Ccr2-/- and Rag1-/- mice, antibody-mediated depletion of CD4+ or CD8+ T cells from WT mice diminished paralysis. These results indicate that immune cell recruitment to the spinal cord promotes EV-D68-associated paralysis and illuminate potential new targets for therapeutic intervention.","journal":"Journal of Clinical Investigation","year":2025,"id":523523,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"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":274867,"name":"Lan Lan","orcid":"0000-0002-8045-7654","position":1,"is_corresponding":false},{"id":1396450,"name":"Sarah Maya","orcid":null,"position":2,"is_corresponding":false},{"id":251862,"name":"Jennifer E. Jones","orcid":"0000-0002-9970-1063","position":3,"is_corresponding":false},{"id":1396451,"name":"Isabella E. Bosco","orcid":null,"position":4,"is_corresponding":false},{"id":236968,"name":"John V. Williams","orcid":"0000-0001-8377-5175","position":5,"is_corresponding":false},{"id":521847,"name":"Megan Culler Freeman","orcid":"0000-0003-3389-6731","position":6,"is_corresponding":false},{"id":533157,"name":"Terence S. Dermody","orcid":"0000-0003-1853-8741","position":7,"is_corresponding":false},{"id":420754,"name":"Mikal A. Woods Acevedo","orcid":"0000-0002-2841-7321","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40459936","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":[]}