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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection.

Authors: Tse, Longping V; Meganck, Rita M; Araba, Kenza C; Yount, Boyd L; Shaffer, Kendall M; Hou, Yixuan J; Munt, Jennifer E; Adams, Lily E; Wykoff, Jason A; Morowitz, Jeremy M; Dong, Stephanie; Magness, Scott T; Marzluff, William F; Gonzalez, Liara M; Ehre, Camille; Baric, Ralph S

Published In Proc Natl Acad Sci U S A, (2022 May 03)

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.

PubMed ID: 35476513 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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