Article ; Online: Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection.
2021 Volume 12, Issue 1, Page(s) 5809
Abstract: SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and ... ...
| Abstract | SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer a unique opportunity to study the early steps of viral infection and screening antivirals. These models are not dedicated to investigate how the virus reaches the brain. However, they allow validating the early tropism of the virus in the lungs and demonstrating that SARS-CoV-2 could infect the brainstem and the cerebellum, mainly by targeting granular neurons. Viral infection induces specific interferon and innate immune responses with patterns specific to each organ, along with cell death by apoptosis, necroptosis, and pyroptosis. Overall, our data illustrate the potential of rapid modeling of complex tissue-level interactions during infection by a newly emerged virus. |
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| MeSH term(s) | Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/pharmacology ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Alveolar Epithelial Cells/virology ; Animals ; Antiviral Agents/pharmacology ; Brain Stem/cytology ; Brain Stem/immunology ; Brain Stem/pathology ; Brain Stem/virology ; Cricetinae ; Immunity, Innate ; Inflammation ; Lung/cytology ; Lung/immunology ; Lung/pathology ; Lung/virology ; Models, Biological ; Neurons/virology ; Organ Culture Techniques ; Regulated Cell Death ; SARS-CoV-2/drug effects ; SARS-CoV-2/pathogenicity ; Viral Tropism |
| Chemical Substances | Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX) |
| Language | English |
| Publishing date | 2021-10-04 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-021-26096-z |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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