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Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq. | LitMetric

AI Article Synopsis

  • Researchers used a technique called Perturb-seq to study how disabling certain host factors affects SARS-CoV-2 infection in human lung cells.
  • They discovered that only a small number of these host factors significantly altered the infection process and the body’s immune response.
  • Notably, they identified specific factors, like IκBα and translation factors EIF4E2 and EIF4H, as critical for early stages of the infection, advancing understanding of how the virus interacts with host cells.

Article Abstract

Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation of their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with a single-cell readout, to investigate how inactivation of host factors changes the course of SARS-CoV-2 infection and the host response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts in the stages of infection and modulations of the interferon response. However, only a small percentage of host factors showed such phenotypes upon perturbation. We further identified the NF-κB inhibitor IκBα (NFKBIA), as well as the translation factors EIF4E2 and EIF4H as strong host dependency factors acting early in infection. Overall, our study provides massively parallel functional characterization of host factors of SARS-CoV-2 and quantitatively defines their roles both in virus-infected and bystander cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558542PMC
http://dx.doi.org/10.1038/s41467-023-41788-4DOI Listing

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