Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns.
SARS-CoV-2 attaches to angiotensin-converting enzyme 2 (ACE2) to gain entry into cells after which the spike protein is cleaved by the transmembrane serine protease 2 (TMPRSS2) to facilitate viral-host membrane fusion. ACE2 and TMPRSS2 expression profiles have been analyzed at the genomic, transcrip...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010340 |
| _version_ | 1818285719975624704 |
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| author | Ilhan Tomris Kim M Bouwman Youri Adolfs Danny Noack Roosmarijn van der Woude Gius Kerster Sander Herfst Rogier W Sanders Marit J van Gils Geert-Jan Boons Bart L Haagmans R Jeroen Pasterkamp Barry Rockx Robert P de Vries |
| author_facet | Ilhan Tomris Kim M Bouwman Youri Adolfs Danny Noack Roosmarijn van der Woude Gius Kerster Sander Herfst Rogier W Sanders Marit J van Gils Geert-Jan Boons Bart L Haagmans R Jeroen Pasterkamp Barry Rockx Robert P de Vries |
| author_sort | Ilhan Tomris |
| collection | DOAJ |
| description | SARS-CoV-2 attaches to angiotensin-converting enzyme 2 (ACE2) to gain entry into cells after which the spike protein is cleaved by the transmembrane serine protease 2 (TMPRSS2) to facilitate viral-host membrane fusion. ACE2 and TMPRSS2 expression profiles have been analyzed at the genomic, transcriptomic, and single-cell RNAseq levels. However, transcriptomic data and actual protein validation convey conflicting information regarding the distribution of the biologically relevant protein receptor in whole tissues. To describe the organ-level architecture of receptor expression, related to the ability of ACE2 and TMPRSS2 to mediate infectivity, we performed a volumetric analysis of whole Syrian hamster lung lobes. Lung tissue of infected and control animals was stained using antibodies against ACE2 and TMPRSS2, combined with SARS-CoV-2 nucleoprotein staining. This was followed by light-sheet microscopy imaging to visualize their expression and related infection patterns. The data demonstrate that infection is restricted to sites containing both ACE2 and TMPRSS2, the latter is expressed in the primary and secondary bronchi whereas ACE2 is predominantly observed in the bronchioles and alveoli. Conversely, infection completely overlaps where ACE2 and TMPRSS2 co-localize in the tertiary bronchi, bronchioles, and alveoli. |
| first_indexed | 2024-12-13T01:13:11Z |
| format | Article |
| id | doaj.art-dcc13b37132847f5b458e98303166130 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T01:13:11Z |
| publishDate | 2022-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-dcc13b37132847f5b458e983031661302022-12-22T00:04:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-03-01183e101034010.1371/journal.ppat.1010340Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns.Ilhan TomrisKim M BouwmanYouri AdolfsDanny NoackRoosmarijn van der WoudeGius KersterSander HerfstRogier W SandersMarit J van GilsGeert-Jan BoonsBart L HaagmansR Jeroen PasterkampBarry RockxRobert P de VriesSARS-CoV-2 attaches to angiotensin-converting enzyme 2 (ACE2) to gain entry into cells after which the spike protein is cleaved by the transmembrane serine protease 2 (TMPRSS2) to facilitate viral-host membrane fusion. ACE2 and TMPRSS2 expression profiles have been analyzed at the genomic, transcriptomic, and single-cell RNAseq levels. However, transcriptomic data and actual protein validation convey conflicting information regarding the distribution of the biologically relevant protein receptor in whole tissues. To describe the organ-level architecture of receptor expression, related to the ability of ACE2 and TMPRSS2 to mediate infectivity, we performed a volumetric analysis of whole Syrian hamster lung lobes. Lung tissue of infected and control animals was stained using antibodies against ACE2 and TMPRSS2, combined with SARS-CoV-2 nucleoprotein staining. This was followed by light-sheet microscopy imaging to visualize their expression and related infection patterns. The data demonstrate that infection is restricted to sites containing both ACE2 and TMPRSS2, the latter is expressed in the primary and secondary bronchi whereas ACE2 is predominantly observed in the bronchioles and alveoli. Conversely, infection completely overlaps where ACE2 and TMPRSS2 co-localize in the tertiary bronchi, bronchioles, and alveoli.https://doi.org/10.1371/journal.ppat.1010340 |
| spellingShingle | Ilhan Tomris Kim M Bouwman Youri Adolfs Danny Noack Roosmarijn van der Woude Gius Kerster Sander Herfst Rogier W Sanders Marit J van Gils Geert-Jan Boons Bart L Haagmans R Jeroen Pasterkamp Barry Rockx Robert P de Vries Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns. PLoS Pathogens |
| title | Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns. |
| title_full | Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns. |
| title_fullStr | Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns. |
| title_full_unstemmed | Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns. |
| title_short | Distinct spatial arrangements of ACE2 and TMPRSS2 expression in Syrian hamster lung lobes dictates SARS-CoV-2 infection patterns. |
| title_sort | distinct spatial arrangements of ace2 and tmprss2 expression in syrian hamster lung lobes dictates sars cov 2 infection patterns |
| url | https://doi.org/10.1371/journal.ppat.1010340 |
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