DESCRIPTION:

This gene set represents host genes that are required for SARS-CoV-2 infection. The genes were identified by a CRISPR screen in alveolar basal epithelial carcinoma cells. This set represents the top 100 scoring genes at a low multiplicity of infection, moi 0.01. Gene symbols of ranked genes in supplemental table 1 were converted to HGNC identifiers. Symbols that could not be unambiguously converted were omitted from the set.

LABEL:

Host genes at low moi

SCORE TYPE:

Binary

DATE ADDED:

2021-05-17

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Zharko Daniloski, Tristan X Jordan, Hans-Hermann Wessels, Daisy A Hoagland, Silva Kasela, Mateusz Legut, Silas Maniatis, Eleni P Mimitou, Lu Lu, Evan Geller, Oded Danziger, Brad R Rosenberg, Hemali Phatnani, Peter Smibert, Tuuli Lappalainen, Benjamin R tenOever, Neville E Sanjana

TITLE:

Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells.

JOURNAL:

Cell 01 2021, Vol 184, pp. 92-105.e16

ABSTRACT:

To better understand host-virus genetic dependencies and find potential therapeutic targets for COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors required for SARS-CoV-2 viral infection of human alveolar epithelial cells. Top-ranked genes cluster into distinct pathways, including the vacuolar ATPase proton pump, Retromer, and Commander complexes. We validate these gene targets using several orthogonal methods such as CRISPR knockout, RNA interference knockdown, and small-molecule inhibitors. Using single-cell RNA-sequencing, we identify shared transcriptional changes in cholesterol biosynthesis upon loss of top-ranked genes. In addition, given the key role of the ACE2 receptor in the early stages of viral entry, we show that loss of RAB7A reduces viral entry by sequestering the ACE2 receptor inside cells. Overall, this work provides a genome-scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection. PUBMED: 33147445
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