ArticleProceedings of the National Academy of Sciences of the United States of America2022
Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Rab10 coordinates SADS-CoV non-lytic egress through the ERGIC-TGN-lysosome trafficking pathway.PLoS pathogens · 2026Article
- CRISPR-based screening of host factors in veterinary viral infections: from target discovery to host-directed antiviral strategies.Frontiers in veterinary science · 2026Review
- UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.Nature communications · 2025Article
- Identification and characterization of a nonpeptidic cyclophilin ligand with antiviral activity against feline and porcine α-coronaviruses.Veterinary research · 2025Article
- Temporal multi-omics analysis of COVID-19 in end-stage kidney disease.Cell genomics · 2025Article
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- Molecular breeding of pigs in the genome editing era.Genetics, selection, evolution : GSE · 2025Review
- Host factor PLAC8 is required for pancreas infection by SARS-CoV-2.Communications medicine · 2025Article
- Swine Acute Diarrhea Syndrome Coronavirus: An Overview of Virus Structure and Virus-Host Interactions.Animals : an open access journal from MDPI · 2025Review
- Review
- Functional dissection of the spike glycoprotein S1 subunit and identification of cellular cofactors for regulation of swine acute diarrhea syndrome coronavirus entry.Journal of virology · 2024Article
- Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis.Cell reports · 2024Article
- Research Advances on Swine Acute Diarrhea Syndrome Coronavirus.Animals : an open access journal from MDPI · 2024Review
- Prevention and Control of Swine Enteric Coronaviruses in China: A Review of Vaccine Development and Application.Vaccines · 2023Review
- Identification of TMEM53 as a novel SADS-CoV restriction factor that targets viral RNA-dependent RNA polymerase.Emerging microbes & infections · 2023Article
- Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.Cell host & microbe · 2023Article
- A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus.Science translational medicine · 2023Article
- Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists.Biomaterials · 2023Article
- Article
- Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells.The EMBO journal · 2022Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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