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Long-Term Modeling of SARS-CoV-2 Infection of In Vitro Cultured Polarized Human Airway Epithelium.
Hao, Siyuan; Ning, Kang; Kuz, Cagla Aksu; Vorhies, Kai; Yan, Ziying; Qiu, Jianming.
  • Hao S; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Ning K; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Kuz CA; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • Vorhies K; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, 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 ; 11(6)2020 11 06.
Article in English | MEDLINE | ID: covidwho-930294
Semantic information from SemMedBD (by NLM)
1. Epithelium LOCATION_OF COVID-19
Subject
Epithelium
Predicate
LOCATION_OF
Object
COVID-19
2. Airway structure PART_OF Homo sapiens
Subject
Airway structure
Predicate
PART_OF
Object
Homo sapiens
3. COVID-19 COEXISTS_WITH Acute Lung Injury
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Acute Lung Injury
4. Bronchus and lung PART_OF Donor person
Subject
Bronchus and lung
Predicate
PART_OF
Object
Donor person
5. Clara cell LOCATION_OF Virus Replication
Subject
Clara cell
Predicate
LOCATION_OF
Object
Virus Replication
6. Basal Cell LOCATION_OF Virus Replication
Subject
Basal Cell
Predicate
LOCATION_OF
Object
Virus Replication
7. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
8. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
9. Epithelium LOCATION_OF 2019 novel coronavirus
Subject
Epithelium
Predicate
LOCATION_OF
Object
2019 novel coronavirus
10. Epithelium LOCATION_OF COVID-19
Subject
Epithelium
Predicate
LOCATION_OF
Object
COVID-19
11. Airway structure PART_OF Homo sapiens
Subject
Airway structure
Predicate
PART_OF
Object
Homo sapiens
12. COVID-19 COEXISTS_WITH Acute Lung Injury
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Acute Lung Injury
13. Bronchus and lung PART_OF Donor person
Subject
Bronchus and lung
Predicate
PART_OF
Object
Donor person
14. Clara cell LOCATION_OF Virus Replication
Subject
Clara cell
Predicate
LOCATION_OF
Object
Virus Replication
15. Basal Cell LOCATION_OF Virus Replication
Subject
Basal Cell
Predicate
LOCATION_OF
Object
Virus Replication
16. 2019 novel coronavirus CAUSES COVID-19
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
COVID-19
17. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
18. Epithelium LOCATION_OF 2019 novel coronavirus
Subject
Epithelium
Predicate
LOCATION_OF
Object
2019 novel coronavirus
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates throughout human airways. The polarized human airway epithelium (HAE) cultured at an airway-liquid interface (HAE-ALI) is an in vitro model mimicking the in vivo human mucociliary airway epithelium and supports the replication of SARS-CoV-2. Prior studies characterized only short-period SARS-CoV-2 infection in HAE. In this study, continuously monitoring the SARS-CoV-2 infection in HAE-ALI cultures for a long period of up to 51 days revealed that SARS-CoV-2 infection was long lasting with recurrent replication peaks appearing between an interval of approximately 7 to 10 days, which was consistent in all the tested HAE-ALI cultures derived from 4 lung bronchi of independent donors. We also identified that SARS-CoV-2 does not infect HAE from the basolateral side, and the dominant SARS-CoV-2 permissive epithelial cells are ciliated cells and goblet cells, whereas virus replication in basal cells and club cells was not detected. Notably, virus infection immediately damaged the HAE, which is demonstrated by dispersed zonula occludens-1 (ZO-1) expression without clear tight junctions and partial loss of cilia. Importantly, we identified that SARS-CoV-2 productive infection of HAE requires a high viral load of >2.5 × 105 virions per cm2 of epithelium. Thus, our studies highlight the importance of a high viral load and that epithelial renewal initiates and maintains a recurrent infection of HAE with SARS-CoV-2.IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to >35 million confirmed cases and >1 million fatalities worldwide. SARS-CoV-2 mainly replicates in human airway epithelia in COVID-19 patients. In this study, we used in vitro cultures of polarized human bronchial airway epithelium to model SARS-CoV-2 replication for a period of 21 to 51 days. We discovered that in vitro airway epithelial cultures endure a long-lasting SARS-CoV-2 propagation with recurrent peaks of progeny virus release at an interval of approximately 7 to 10 days. Our study also revealed that SARS-CoV-2 infection causes airway epithelia damage with disruption of tight junction function and loss of cilia. Importantly, SARS-CoV-2 exhibits a polarity of infection in airway epithelium only from the apical membrane; it infects ciliated and goblet cells but not basal and club cells. Furthermore, the productive infection of SARS-CoV-2 requires a high viral load of over 2.5 × 105 virions per cm2 of epithelium. Our study highlights that the proliferation of airway basal cells and regeneration of airway epithelium may contribute to the recurrent infections.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Mucosa / Betacoronavirus / Models, Biological Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: MBio.02852-20

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Mucosa / Betacoronavirus / Models, Biological Limits: Humans Language: English Year: 2020 Document Type: Article Affiliation country: MBio.02852-20