Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 06, 2023
- Source ID
- 10.1038/s41467-023-41788-4
Entities
People
- Aidan H. Mcmorrow
- Andreas S Puschnik
- Chun Jimmie Ye
- James K Nuñez
- Jamin Liu
- Janie R. Byrum
- Jonathan Weissman
- Joseph L. Derisi
- Joseph M Replogle
- Juliane Winkler
- Manuel D Leonetti
- Marco Y. Hein
- Matthew B. Frieman
- Matthew T. Laurie
- Oren S Rosenberg
- Sara Sunshine
- Shoshana Zha
- Xiaojie Qiu
Organizations
- United States Department of Defense