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10.1073/pnas.2118126119

http://scihub22266oqcxt.onion/10.1073/pnas.2118126119
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suck abstract from ncbi


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pmid35476513      Proc+Natl+Acad+Sci+U+S+A 2022 ; 119 (18): e2118126119
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  • Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection #MMPMID35476513
  • Tse LV; Meganck RM; Araba KC; Yount BL; Shaffer KM; Hou YJ; Munt JE; Adams LE; Wykoff JA; Morowitz JM; Dong S; Magness ST; Marzluff WF; Gonzalez LM; Ehre C; Baric RS
  • Proc Natl Acad Sci U S A 2022[May]; 119 (18): e2118126119 PMID35476513show ga
  • 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.
  • |*Alphacoronavirus/genetics[MESH]
  • |*Coronavirus Infections/epidemiology[MESH]
  • |*Swine Diseases[MESH]
  • |Animals[MESH]
  • |Clustered Regularly Interspaced Short Palindromic Repeats/genetics[MESH]


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