{"doi":"10.17615/qvw2-wm33","title":"Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection","abstract":"Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV.","journal":"UNC Libraries","year":2022,"id":310112,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":874024,"name":"Jason A. Wykoff","orcid":"0000-0002-0201-5420","position":1,"is_corresponding":false},{"id":816366,"name":"Stephanie Dong","orcid":"0000-0002-0318-5261","position":2,"is_corresponding":false},{"id":355496,"name":"Jennifer E. Munt","orcid":"0000-0002-1169-025X","position":3,"is_corresponding":false},{"id":453100,"name":"Liara M. Gonzalez","orcid":"0000-0003-3972-2812","position":4,"is_corresponding":false},{"id":874023,"name":"Kendall M. Shaffer","orcid":"0000-0002-1052-2975","position":5,"is_corresponding":false},{"id":874526,"name":"Jeremy M. Morowitz","orcid":null,"position":6,"is_corresponding":false},{"id":60558,"name":"Scott T. Magness","orcid":"0000-0002-2746-1224","position":7,"is_corresponding":false},{"id":104944,"name":"Longping V. Tse","orcid":"0000-0001-7582-8396","position":8,"is_corresponding":false},{"id":5947,"name":"Yixuan J. Hou","orcid":"0000-0002-8323-7243","position":9,"is_corresponding":false},{"id":277822,"name":"Rita M. Meganck","orcid":"0000-0003-2799-3754","position":10,"is_corresponding":false},{"id":105503,"name":"Boyd L. Yount","orcid":"0000-0002-6099-8429","position":11,"is_corresponding":false},{"id":107105,"name":"Camille Ehré","orcid":"0000-0002-0046-0096","position":12,"is_corresponding":false},{"id":274107,"name":"William F. Marzluff","orcid":"0000-0003-3635-4073","position":13,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":14,"is_corresponding":false},{"id":562550,"name":"Kenza C. Araba","orcid":null,"position":15,"is_corresponding":false},{"id":109139,"name":"Lily E. Adams","orcid":"0000-0001-7780-9973","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:15.860993Z","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":[]}