jywygjj

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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 that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.
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?:creator	<https://research.tib.eu/covid-19/entity/Hekman%2C_Ryan_M%3B_Hume%2C_Adam_J%3B_Goel%2C_Raghuveera_Kumar%3B_Abo%2C_Kristine_M%3B_Huang%2C_Jessie%3B_Blum%2C_Benjamin_C%3B_Werder%2C_Rhiannon_B%3B_Suder%2C_Ellen_L%3B_Paul%2C_Indranil%3B_Phanse%2C_Sadhna%3B_Youssef%2C_Ahmed%3B_Alysandratos%2C_Konstantinos_D%3B_Padhorny%2C_Dzmitry%3B_Ojha%2C_Sandeep%3B_Mora-Martin%2C_Alexandra%3B_Kretov%2C_Dmitry%3B_Ash%2C_Peter_E_A%3B_Verma%2C_Mamta%3B_Zhao%2C_Jian%3B_Patten%2C_J_J%3B_Villacorta-Martin%2C_Carlos%3B_Bolzan%2C_Dante%3B_Perea-Resa%2C_Carlos%3B_Bullitt%2C_Esther%3B_Hinds%2C_Anne%3B_Tilston-Lunel%2C_Andrew%3B_Varelas%2C_Xaralabos%3B_Farhangmehr%2C_Shaghayegh%3B_Braunschweig%2C_Ulrich%3B_Kwan%2C_Julian_H%3B_McComb%2C_Mark%3B_Basu%2C_Avik%3B_Saeed%2C_Mohsan%3B_Perissi%2C_Valentina%3B_Burks%2C_Eric_J%3B_Layne%2C_Matthew_D%3B_Connor%2C_John_H%3B_Davey%2C_Robert%3B_Cheng%2C_Ji-Xin%3B_Wolozin%2C_Benjamin_L%3B_Blencowe%2C_Benjamin_J%3B_Wuchty%2C_Stefan%3B_Lyons%2C_Shawn_M%3B_Kozakov%2C_Dima%3B_Cifuentes%2C_Daniel%3B_Blower%2C_Michael%3B_Kotton%2C_Darrell_N%3B_Wilson%2C_Andrew_A%3B_M%C3%BChlberger%2C_Elke%3B_Emili%2C_Andrew> <https://research.tib.eu/covid-19/entity/Hekman%2C_Ryan_M%3B_Hume%2C_Adam_J%3B_Goel%2C_Raghuveera_Kumar%3B_Abo%2C_Kristine_M%3B_Huang%2C_Jessie%3B_Blum%2C_Benjamin_C%3B_Werder%2C_Rhiannon_Bree%3B_Suder%2C_Ellen_L%3B_Paul%2C_Indranil%3B_Phanse%2C_Sadhna%3B_Youssef%2C_Ahmed%3B_Alysandratos%2C_Kostantinos_D%3B_Padhorny%2C_Dzmitry%3B_Ojha%2C_Sandeep%3B_Mora-Martin%2C_Alexandra%3B_Kretov%2C_Dmitry%3B_Ash%2C_Peter%3B_Varma%2C_Mamta%3B_Zhao%2C_Jian%3B_Patten%2C_J_J%3B_Villacorta-Martin%2C_Carlos%3B_Bolzan%2C_Dante%3B_Perea-Resa%2C_Carlos%3B_Bullitt%2C_Esther%3B_Hinds%2C_Anne%3B_Tilston-Lunel%2C_Andrew%3B_Varelas%2C_Xaralabos%3B_Farhangmehr%2C_Shaghayegh%3B_Braunschweig%2C_Ulrich%3B_Kwan%2C_Julian_H%3B_McComb%2C_Mark%3B_Basu%2C_Avik%3B_Saeed%2C_Mohsan%3B_Perissi%2C_Valentina%3B_Burks%2C_Eric_J%3B_Layne%2C_Matthew_D%3B_Connor%2C_John_H%3B_Davey%2C_Robert%3B_Cheng%2C_Ji-Xin%3B_Wolozin%2C_Benjamin_L%3B_Blencowe%2C_Benjamin_J%3B_Wuchty%2C_Stefan%3B_Lyons%2C_Shawn_M%3B_Kozakov%2C_Dima%3B_Cifuentes%2C_Daniel%3B_Blower%2C_Michael%3B_Kotton%2C_Darrell_N%3B_Wilson%2C_Andrew_A%3B_M%C3%BChlberger%2C_Elke%3B_Emili%2C_Andrew>
?:journal	Mol._cell Mol_Cell
?:license	unk
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
is ?:relation_isRelatedTo_publication of	<https://research.tib.eu/covid-19/entity/8jywygjj_HAS_C0042776_INTERACTS_WITH_C5203676> <https://research.tib.eu/covid-19/entity/8jywygjj_HAS_C5203676_CAUSES_C5203670>
?:source	WHO
?:title	Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#1023719 #933377
?:year	2020 2021

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 that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.

is ?:annotates of