ga3a2o56

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?: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 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.
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?:creator	<https://research.tib.eu/covid-19/entity/Daniloski%2C_Z.%3B_Jordan%2C_T._X.%3B_Wessels%2C_H._H.%3B_Hoagland%2C_D._A.%3B_Kasela%2C_S.%3B_Legut%2C_M.%3B_Maniatis%2C_S.%3B_Mimitou%2C_E._P.%3B_Lu%2C_L.%3B_Geller%2C_E.%3B_Danziger%2C_O.%3B_Rosenberg%2C_B._R.%3B_Phatnani%2C_H.%3B_Smibert%2C_P.%3B_Lappalainen%2C_T.%3B_tenOever%2C_B._R.%3B_Sanjana%2C_N._E.> <https://research.tib.eu/covid-19/entity/Daniloski%2C_Zharko%3B_Jordan%2C_Tristan_X%3B_Wessels%2C_Hans-Hermann%3B_Hoagland%2C_Daisy_A%3B_Kasela%2C_Silva%3B_Legut%2C_Mateusz%3B_Maniatis%2C_Silas%3B_Mimitou%2C_Eleni_P%3B_Lu%2C_Lu%3B_Geller%2C_Evan%3B_Danziger%2C_Oded%3B_Rosenberg%2C_Brad_R%3B_Phatnani%2C_Hemali%3B_Smibert%2C_Peter%3B_Lappalainen%2C_Tuuli%3B_tenOever%2C_Benjamin_R%3B_Sanjana%2C_Neville_E>
?:journal	Cell
?:license	unk
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
?:source	WHO
?:title	Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#1064907 #910308
?:year	2021

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Value

?: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
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.

is ?:annotates of