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The SARS-CoV-2 Transcriptome and the Dynamics of the S Gene Furin Cleavage Site in Primary Human Airway Epithelia.
Zou, Wei; Xiong, Min; Hao, Siyuan; Zhang, Elizabeth Yan; Baumlin, Nathalie; Kim, Michael D; Salathe, Matthias; Yan, Ziying; Qiu, Jianming.
  • Zou W; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
  • Xiong M; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Hao S; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Zhang EY; GeneGoCell Inc., San Diego, California, USA.
  • Baumlin N; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Kim MD; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Salathe M; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Yan Z; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA ziying-yan@uiowa.edu jqiu@kumc.edu.
  • Qiu J; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA ziying-yan@uiowa.edu jqiu@kumc.edu.
mBio ; 12(3)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1225698
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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Semantic information from SemMedBD (by NLM)
1. Transcriptome PART_OF 2019 novel coronavirus
Subject
Transcriptome
Predicate
PART_OF
Object
2019 novel coronavirus
2. Epithelium LOCATION_OF Transcriptome
Subject
Epithelium
Predicate
LOCATION_OF
Object
Transcriptome
3. Peptide Hydrolases PART_OF Cells
Subject
Peptide Hydrolases
Predicate
PART_OF
Object
Cells
4. Patients LOCATION_OF Peptide Hydrolases
Subject
Patients
Predicate
LOCATION_OF
Object
Peptide Hydrolases
5. Polypeptides PART_OF 2019 novel coronavirus
Subject
Polypeptides
Predicate
PART_OF
Object
2019 novel coronavirus
6. Vero Cells LOCATION_OF 2019 novel coronavirus
Subject
Vero Cells
Predicate
LOCATION_OF
Object
2019 novel coronavirus
7. Transcriptome PART_OF Vero Cells
Subject
Transcriptome
Predicate
PART_OF
Object
Vero Cells
8. Lung diseases PROCESS_OF Donor person
Subject
Lung diseases
Predicate
PROCESS_OF
Object
Donor person
9. Virion LOCATION_OF Dynamics
Subject
Virion
Predicate
LOCATION_OF
Object
Dynamics
10. Airway structure PART_OF Homo sapiens
Subject
Airway structure
Predicate
PART_OF
Object
Homo sapiens
11. Vitronecti PART_OF C5203676
Subject
Vitronecti
Predicate
PART_OF
Object
C5203676
12. Epithelial Cells LOCATION_OF Cytokinesis
Subject
Epithelial Cells
Predicate
LOCATION_OF
Object
Cytokinesis
13. Transcriptome PART_OF 2019 novel coronavirus
Subject
Transcriptome
Predicate
PART_OF
Object
2019 novel coronavirus
14. Epithelium LOCATION_OF Transcriptome
Subject
Epithelium
Predicate
LOCATION_OF
Object
Transcriptome
15. Peptide Hydrolases PART_OF Cells
Subject
Peptide Hydrolases
Predicate
PART_OF
Object
Cells
16. Patients LOCATION_OF Peptide Hydrolases
Subject
Patients
Predicate
LOCATION_OF
Object
Peptide Hydrolases
17. Polypeptides PART_OF 2019 novel coronavirus
Subject
Polypeptides
Predicate
PART_OF
Object
2019 novel coronavirus
18. Vero Cells LOCATION_OF 2019 novel coronavirus
Subject
Vero Cells
Predicate
LOCATION_OF
Object
2019 novel coronavirus
19. Transcriptome PART_OF Vero Cells
Subject
Transcriptome
Predicate
PART_OF
Object
Vero Cells
20. Lung diseases PROCESS_OF Donor person
Subject
Lung diseases
Predicate
PROCESS_OF
Object
Donor person
21. Virion LOCATION_OF Dynamics
Subject
Virion
Predicate
LOCATION_OF
Object
Dynamics
22. Airway structure PART_OF Homo sapiens
Subject
Airway structure
Predicate
PART_OF
Object
Homo sapiens
23. Vitronectin, human PART_OF 2019 novel coronavirus
Subject
Vitronectin, human
Predicate
PART_OF
Object
2019 novel coronavirus
24. Epithelial Cells LOCATION_OF Cytokinesis
Subject
Epithelial Cells
Predicate
LOCATION_OF
Object
Cytokinesis
ABSTRACT
The spike (S) polypeptide of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary that contains a furin cleavage site (FCS), 682RRAR↓S686 Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, it acquired deletions surrounding the FCS. We studied the viral transcriptome in Vero cell-derived SARS-CoV-2-infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability of the FCS. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the FCS region a 12 amino acid deletion (678TNSPRRAR↓SVAS689) that contains the underlined FCS and a 5 amino acid deletion (675QTQTN679) that is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions from 11 infected HAE-ALI cultures of both healthy and lung disease donors revealed that the selective pressure for the FCS maintains the FCS stably in 9 HAE-ALI cultures but with 2 exceptions, in which the FCS deletions are retained at a high rate of >40% after infection of ≥13 days. Our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is likely donor dependent.IMPORTANCE Polarized human airway epithelia at an air-liquid interface (HAE-ALI) are an in vitro model that supports efficient infection of SARS-CoV-2. The spike (S) protein of SARS-CoV-2 contains a furin cleavage site (FCS) at the boundary of the S1 and S2 domains which distinguishes it from SARS-CoV. However, FCS deletion mutants have been identified in patients and in vitro cell cultures, and how the airway epithelial cells maintain the unique FCS remains unknown. We found that HAE-ALI cultures were capable of suppressing two prevalent FCS deletion mutants (Δ678TNSPRRAR↓SVAS689 and Δ675QTQTN679) that were selected during propagation in Vero cells. While such suppression was observed in 9 out of 11 of the tested HAE-ALI cultures derived from independent donors, 2 exceptions that retained a high rate of FCS deletions were also found. Our results present evidence of the donor-dependent properties of human airway epithelia in the evolution of the FCS during infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Bronchi / Respiratory Mucosa / Furin / Transcriptome / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: MBio.01006-21

Full text: Available Collection: International databases Database: MEDLINE Main subject: Bronchi / Respiratory Mucosa / Furin / Transcriptome / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: MBio.01006-21