ArticleThe EMBO journal2022
Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- COMMD3 coordinates mannose-6-phosphate receptor trafficking to sustain lysosomal protease maturation.Research square · 2026Article
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.Nature communications · 2025Article
- Temporal multi-omics analysis of COVID-19 in end-stage kidney disease.Cell genomics · 2025Article
- Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19.BMC medical genomics · 2025Article
- Host factor PLAC8 is required for pancreas infection by SARS-CoV-2.Communications medicine · 2025Article
- A data-mining analysis of host solute carrier family proteins in SARS-CoV-2 infection with reference to brain endothelial cells and the blood-brain barrier in COVID-19.Frontiers in neurology · 2025Article
- Molecular analysis of long COVID and new-onset diabetes mellitus: pathobiological relationships and current mechanistic views.Frontiers in endocrinology · 2025Review
- Review
- IGSF1: a biomarker for predicting prognosis, immunotherapy response, and drug candidates in COVID-19 combined hepatocellular carcinoma.Discover oncology · 2024Article
- Transcriptional pathways of terminal differentiation in high- and low-density blood granulocytes in sepsis.Journal of inflammation (London, England) · 2024Article
- Review
- GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.Briefings in bioinformatics · 2024Article
- Plac8-ERK pathway modulation of monocyte function in sepsis.Cell death discovery · 2024Article
- 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
- SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024Review
- Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis.Cell reports · 2024Article
- Genetic determinants of IgG antibody response to COVID-19 vaccination.American journal of human genetics · 2024Article
- DDX5 inhibits type I IFN production by promoting degradation of TBK1 and disrupting formation of TBK1 - TRAF3 complex.Cellular and molecular life sciences : CMLS · 2023Article
- Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Better understanding on interactions between SARS-CoV-2 and host cells should help to identify host factors that may be targetable to combat infection and COVID-19 pathology. To this end, we have conducted a genome-wide CRISPR/Cas9-based loss-of-function screen in human lung cancer cells infected with SARS-CoV-2-pseudotyped lentiviruses. Our results recapitulate many findings from previous screens that used full SARS-CoV-2 viruses, but also unveil two novel critical host factors: the lysosomal efflux transporter SPNS1 and the plasma and lysosomal membrane protein PLAC8. Functional experiments with full SARS-CoV-2 viruses confirm that loss-of-function of these genes impairs viral entry. We find that PLAC8 is a key limiting host factor, whose overexpression boosts viral infection in eight different human lung cancer cell lines. Using single-cell RNA-Seq data analyses, we demonstrate that PLAC8 is highly expressed in ciliated and secretory cells of the respiratory tract, as well as in gut enterocytes, cell types that are highly susceptible to SARS-CoV-2 infection. Proteomics and cell biology studies suggest that PLAC8 and SPNS1 regulate the autophagolysosomal compartment and affect the intracellular fate of endocytosed virions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.