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Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium.
bioRxiv ; 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-900750
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. Airway structure PART_OF Homo sapiens
Subject
Airway structure
Predicate
PART_OF
Object
Homo sapiens
2. Severe Acute Respiratory Syndrome COEXISTS_WITH Acute Lung Injury
Subject
Severe Acute Respiratory Syndrome
Predicate
COEXISTS_WITH
Object
Acute Lung Injury
3. Bronchus and lung PART_OF Donor person
Subject
Bronchus and lung
Predicate
PART_OF
Object
Donor person
4. Clara cell LOCATION_OF Virus Replication
Subject
Clara cell
Predicate
LOCATION_OF
Object
Virus Replication
5. Basal Cell LOCATION_OF Virus Replication
Subject
Basal Cell
Predicate
LOCATION_OF
Object
Virus Replication
6. Airway structure PART_OF Homo sapiens
Subject
Airway structure
Predicate
PART_OF
Object
Homo sapiens
7. Severe Acute Respiratory Syndrome COEXISTS_WITH Acute Lung Injury
Subject
Severe Acute Respiratory Syndrome
Predicate
COEXISTS_WITH
Object
Acute Lung Injury
8. Bronchus and lung PART_OF Donor person
Subject
Bronchus and lung
Predicate
PART_OF
Object
Donor person
9. Clara cell LOCATION_OF Virus Replication
Subject
Clara cell
Predicate
LOCATION_OF
Object
Virus Replication
10. Basal Cell LOCATION_OF Virus Replication
Subject
Basal Cell
Predicate
LOCATION_OF
Object
Virus Replication
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. However, previous studies only characterized 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 7-10 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 detectable. 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 × 10 5 virions per cm 2 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.

Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2020 Document Type: Article