{"doi":"10.1101/2025.05.22.655571","title":"Overcoming host restrictions to enable continuous passaging of human noroviruses in human intestinal enteroids","abstract":"Human noroviruses (HuNoVs), the leading cause of viral gastroenteritis, can now be cultivated in human intestinal enteroids (HIEs). However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified host restriction factors that might limit viral passaging. CXCL10, CXCL11, and CCL5 were among the most upregulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. TAK-779 also enhanced replication of GI.1 and GII.17 strains, but not GII.4, suggesting strain-specific host interactions or immune evasion. This breakthrough in passaging provides critical insight into HuNoV-host interactions, establishes a scalable in vitro system for virus propagation, and opens avenues for structural, biochemical and therapeutic studies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556359,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":270535,"name":"Sue E. Crawford","orcid":"0000-0001-8113-3806","position":1,"is_corresponding":false},{"id":270533,"name":"Sasirekha Ramani","orcid":"0000-0001-5631-8534","position":2,"is_corresponding":false},{"id":270537,"name":"B. Vijayalakshmi Ayyar","orcid":"0000-0001-6775-9546","position":3,"is_corresponding":false},{"id":1456037,"name":"Aaya Boussattach","orcid":null,"position":4,"is_corresponding":false},{"id":272739,"name":"Xi‐Lei Zeng","orcid":null,"position":5,"is_corresponding":false},{"id":103449,"name":"Robert L. Atmar","orcid":"0000-0001-9989-6772","position":6,"is_corresponding":false},{"id":1456038,"name":"Hoa Nguyen Phuc","orcid":null,"position":7,"is_corresponding":false},{"id":63736,"name":"Cristian Coarfa","orcid":"0000-0002-4183-4939","position":8,"is_corresponding":false},{"id":270540,"name":"Mary K. Estes","orcid":"0000-0002-4813-4249","position":9,"is_corresponding":false},{"id":850756,"name":"Gurpreet Kaur","orcid":"0000-0002-4883-6099","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:55:08.896385Z","pmid":"40661516","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":[]}