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Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus
A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663187/ https://www.ncbi.nlm.nih.gov/pubmed/23631916 http://dx.doi.org/10.1128/mBio.00165-13 |
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author | Josset, Laurence Menachery, Vineet D. Gralinski, Lisa E. Agnihothram, Sudhakar Sova, Pavel Carter, Victoria S. Yount, Boyd L. Graham, Rachel L. Baric, Ralph S. Katze, Michael G. |
author_facet | Josset, Laurence Menachery, Vineet D. Gralinski, Lisa E. Agnihothram, Sudhakar Sova, Pavel Carter, Victoria S. Yount, Boyd L. Graham, Rachel L. Baric, Ralph S. Katze, Michael G. |
author_sort | Josset, Laurence |
collection | PubMed |
description | A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. |
format | Online Article Text |
id | pubmed-3663187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36631872013-05-28 Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus Josset, Laurence Menachery, Vineet D. Gralinski, Lisa E. Agnihothram, Sudhakar Sova, Pavel Carter, Victoria S. Yount, Boyd L. Graham, Rachel L. Baric, Ralph S. Katze, Michael G. mBio Research Article A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. American Society of Microbiology 2013-04-30 /pmc/articles/PMC3663187/ /pubmed/23631916 http://dx.doi.org/10.1128/mBio.00165-13 Text en Copyright © 2013 Josset et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Josset, Laurence Menachery, Vineet D. Gralinski, Lisa E. Agnihothram, Sudhakar Sova, Pavel Carter, Victoria S. Yount, Boyd L. Graham, Rachel L. Baric, Ralph S. Katze, Michael G. Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus |
title | Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus |
title_full | Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus |
title_fullStr | Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus |
title_full_unstemmed | Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus |
title_short | Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus |
title_sort | cell host response to infection with novel human coronavirus emc predicts potential antivirals and important differences with sars coronavirus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663187/ https://www.ncbi.nlm.nih.gov/pubmed/23631916 http://dx.doi.org/10.1128/mBio.00165-13 |
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