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Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS
BACKGROUND: Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1324951/ https://www.ncbi.nlm.nih.gov/pubmed/16379499 http://dx.doi.org/10.1371/journal.pmed.0030027 |
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author | Nicholls, John M Butany, Jagdish Poon, Leo L. M Chan, Kwok H Beh, Swan Lip Poutanen, Susan Peiris, J. S. Malik Wong, Maria |
author_facet | Nicholls, John M Butany, Jagdish Poon, Leo L. M Chan, Kwok H Beh, Swan Lip Poutanen, Susan Peiris, J. S. Malik Wong, Maria |
author_sort | Nicholls, John M |
collection | PubMed |
description | BACKGROUND: Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans. METHODS AND FINDINGS: We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset. CONCLUSIONS: The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease. |
format | Text |
id | pubmed-1324951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-13249512006-03-06 Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS Nicholls, John M Butany, Jagdish Poon, Leo L. M Chan, Kwok H Beh, Swan Lip Poutanen, Susan Peiris, J. S. Malik Wong, Maria PLoS Med Research Article BACKGROUND: Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans. METHODS AND FINDINGS: We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset. CONCLUSIONS: The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease. Public Library of Science 2006-02 2006-01-03 /pmc/articles/PMC1324951/ /pubmed/16379499 http://dx.doi.org/10.1371/journal.pmed.0030027 Text en Copyright: © 2006 Nicholls et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nicholls, John M Butany, Jagdish Poon, Leo L. M Chan, Kwok H Beh, Swan Lip Poutanen, Susan Peiris, J. S. Malik Wong, Maria Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS |
title | Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS |
title_full | Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS |
title_fullStr | Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS |
title_full_unstemmed | Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS |
title_short | Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS |
title_sort | time course and cellular localization of sars-cov nucleoprotein and rna in lungs from fatal cases of sars |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1324951/ https://www.ncbi.nlm.nih.gov/pubmed/16379499 http://dx.doi.org/10.1371/journal.pmed.0030027 |
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