Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.
The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.0030112 |
| _version_ | 1818926841116753920 |
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| author | Anna de Lang Tracey Baas Thomas Teal Lonneke M Leijten Brandon Rain Albert D Osterhaus Bart L Haagmans Michael G Katze |
| author_facet | Anna de Lang Tracey Baas Thomas Teal Lonneke M Leijten Brandon Rain Albert D Osterhaus Bart L Haagmans Michael G Katze |
| author_sort | Anna de Lang |
| collection | DOAJ |
| description | The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS. |
| first_indexed | 2024-12-20T03:03:31Z |
| format | Article |
| id | doaj.art-06b09a8d07a0490283934cc9563062f5 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-20T03:03:31Z |
| publishDate | 2007-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-06b09a8d07a0490283934cc9563062f52022-12-21T19:55:40ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-08-0138e11210.1371/journal.ppat.0030112Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.Anna de LangTracey BaasThomas TealLonneke M LeijtenBrandon RainAlbert D OsterhausBart L HaagmansMichael G KatzeThe pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.https://doi.org/10.1371/journal.ppat.0030112 |
| spellingShingle | Anna de Lang Tracey Baas Thomas Teal Lonneke M Leijten Brandon Rain Albert D Osterhaus Bart L Haagmans Michael G Katze Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. PLoS Pathogens |
| title | Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. |
| title_full | Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. |
| title_fullStr | Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. |
| title_full_unstemmed | Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. |
| title_short | Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. |
| title_sort | functional genomics highlights differential induction of antiviral pathways in the lungs of sars cov infected macaques |
| url | https://doi.org/10.1371/journal.ppat.0030112 |
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