{"doi":"10.1038/s41541-024-01007-7","title":"CRISPR/Cas9 screens identify key host factors that enhance rotavirus reverse genetics efficacy and vaccine production","abstract":"Rotaviruses pose a significant threat to young children. To identify novel pro- and anti-rotavirus host factors, we performed genome-wide CRISPR/Cas9 screens using rhesus rotavirus and African green monkey cells. Genetic deletion of either SERPINB1 or TMEM236, the top two antiviral factors, in MA104 cells increased virus titers in a rotavirus strain independent manner. Using this information, we optimized the existing rotavirus reverse genetics systems by combining SERPINB1 knockout MA104 cells with a C3P3-G3 helper plasmid. We improved the recovery efficiency and rescued several low-titer rotavirus reporter and mutant strains that prove difficult to rescue otherwise. Furthermore, we demonstrate that TMEM236 knockout in Vero cells supported higher yields of two live-attenuated rotavirus vaccine strains than the parental cell line and represents a more robust vaccine-producing cell substrate. Collectively, we developed a third-generation optimized rotavirus reverse genetics system and generated gene-edited Vero cells as a new substrate for improving rotavirus vaccine production.","journal":"npj Vaccines","year":2024,"id":441427,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"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":748189,"name":"Meagan E. Sullender","orcid":"0000-0001-6666-8650","position":1,"is_corresponding":false},{"id":302322,"name":"Danielle E. Campbell","orcid":"0000-0002-4072-3874","position":2,"is_corresponding":false},{"id":413851,"name":"Leran Wang","orcid":"0009-0003-6928-9893","position":3,"is_corresponding":false},{"id":680249,"name":"Sanghyun Lee","orcid":"0000-0002-0736-1648","position":4,"is_corresponding":false},{"id":910454,"name":"Takahiro Kawagishi","orcid":"0000-0002-8693-1820","position":5,"is_corresponding":false},{"id":238342,"name":"Gaopeng Hou","orcid":"0000-0003-4753-9743","position":6,"is_corresponding":false},{"id":1254483,"name":"Alen Dizdarevic","orcid":null,"position":7,"is_corresponding":false},{"id":296980,"name":"Philippe Jaïs","orcid":null,"position":8,"is_corresponding":false},{"id":298001,"name":"Megan T. Baldridge","orcid":"0000-0002-7030-6131","position":9,"is_corresponding":false},{"id":106970,"name":"Siyuan Ding","orcid":"0000-0002-5338-260X","position":10,"is_corresponding":false},{"id":915361,"name":"Yinxing Zhu","orcid":"0000-0002-6161-7819","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:01:06.281460Z","pmid":"39505878","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":[]}