o68mentl

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?:abstract	Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues which were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.
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?:doi	10.1016/j.molcel.2020.11.028
?:doi	<https://research.tib.eu/covid-19/entity/10.1016/j.molcel.2020.11.028>
?:journal	Mol_Cell
?:license	els-covid
?:pdf_json_files	document_parses/pdf_json/ea2e167aa15ae1e5f6430ed60b0bb75714ad8107.json
?:pmcid	<https://research.tib.eu/covid-19/entity/PMC7674017>
?:pmid	<https://research.tib.eu/covid-19/entity/33259812.0>
?:pmid	33259812.0
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
is ?:relation_isRelatedTo_publication of	<https://research.tib.eu/covid-19/entity/o68mentl_HAS_C5203676_CAUSES_C5203670>
?:sha_id	<https://research.tib.eu/covid-19/entity/ea2e167aa15ae1e5f6430ed60b0bb75714ad8107>
?:source	Elsevier; Medline; PMC
?:title	Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:year	2020-11-19

Property

Value

?:abstract

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues which were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.

is ?:annotates of