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Tytuł pozycji:

Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium.

Tytuł:
Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium.
Autorzy:
Schuler BA; Department of Pediatrics.
Habermann AC; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Plosa EJ; Department of Pediatrics.
Taylor CJ; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Jetter C; Department of Pediatrics.
Negretti NM; Department of Pediatrics.
Kapp ME; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Benjamin JT; Department of Pediatrics.
Gulleman P; Department of Pediatrics.
Nichols DS; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
Braunstein LZ; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Hackett A; Department of Pediatrics.
Koval M; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University, Atlanta, Georgia, USA.
Guttentag SH; Department of Pediatrics.
Blackwell TS; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.; Department of Veterans Affairs Medical Center, Nashville, Tennessee, USA.
Webber SA; Department of Pediatrics.
Banovich NE; Translational Genomics Research Institute, Phoenix, Arizona, USA.
Kropski JA; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.; Department of Veterans Affairs Medical Center, Nashville, Tennessee, USA.
Sucre JM; Department of Pediatrics.; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
Corporate Authors:
Vanderbilt COVID-19 Consortium Cohort
Human Cell Atlas Biological Network
Źródło:
The Journal of clinical investigation [J Clin Invest] 2021 Jan 04; Vol. 131 (1).
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural
Język:
English
Imprint Name(s):
Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
MeSH Terms:
Gene Expression Regulation, Enzymologic*
Alveolar Epithelial Cells/*enzymology
COVID-19/*enzymology
COVID-19/*metabolism
SARS-CoV-2/*metabolism
Serine Endopeptidases/*biosynthesis
Adult ; Aging ; Alveolar Epithelial Cells/pathology ; Alveolar Epithelial Cells/virology ; Animals ; COVID-19/pathology ; Child, Preschool ; Disease Models, Animal ; Female ; Humans ; Infant ; Male ; Mice
References:
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Grant Information:
UL1 TR000445 United States TR NCATS NIH HHS; K08 HL130595 United States HL NHLBI NIH HHS; R01 AI077505 United States AI NIAID NIH HHS; R01 GM108807 United States GM NIGMS NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; R01 HL145372 United States HL NHLBI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; K08 HL143051 United States HL NHLBI NIH HHS; T32 HL094296 United States HL NHLBI NIH HHS; L40 HL138848 United States HL NHLBI NIH HHS; UL1 TR002243 United States TR NCATS NIH HHS; K08 HL133484 United States HL NHLBI NIH HHS; I01 BX002378 United States BX BLRD VA; R01 HL153246 United States HL NHLBI NIH HHS; K08 HL127102 United States HL NHLBI NIH HHS; R38 HL143619 United States HL NHLBI NIH HHS; P30 CA068485 United States CA NCI NIH HHS; P30 AI110527 United States AI NIAID NIH HHS; R01 AI142095 United States AI NIAID NIH HHS; R03 HL154287 United States HL NHLBI NIH HHS
Contributed Indexing:
Keywords: Expression profiling; Pulmonology
Substance Nomenclature:
EC 3.4.21.- (Serine Endopeptidases)
EC 3.4.21.- (TMPRSS2 protein, human)
EC 3.4.21.- (TMPRSS2 protein, mouse)
Entry Date(s):
Date Created: 20201112 Date Completed: 20210115 Latest Revision: 20221202
Update Code:
20240105
PubMed Central ID:
PMC7773394
DOI:
10.1172/JCI140766
PMID:
33180746
Czasopismo naukowe
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.
Update of: bioRxiv. 2020 May 23;:. (PMID: 32511364)

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