The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome
Open accessAbstract
It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-α, IFN-γ, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.
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“Atypical IFNmediated immune responses suggest that type I IFN signaling may be important in the pathogenesis of SARS-CoV (21).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [21]
In the citing paper
“Gene expression signatures for type I and type II IFN responses in the lungs of SARS patients revealed persistent expression of CXCL10, CCL2, IFNAR1, IFNGR1, and CD58.”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [21]
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Metadata
- Authors
- Cameron, M. J., Ran, L., Xu, L., Danesh, A., Bermejo-Martin, J. F., Cameron, C. M., Muller, M. P., Gold, W. L., Richardson, S. E., Poutanen, S. M., Willey, B. M., DeVries, M. E., Fang, Y., Seneviratne, C., Bosinger, S. E., Persad, D., Wilkinson, P., Greller, L. D., Somogyi, R., Humar, A., Keshavjee, S., Louie, M., Loeb, M. B., Brunton, J., McGeer, A. J., the Canadian SARS Research Network, & Kelvin, D. J.
- Affiliations
- University Health Network (CA)
- University of Valladolid, Valladolid, Spain
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- University Health Network, Toronto, Ontario, Canada
- Centre Hospitalier de l’Université de Montréal (CA)
- Biosystemix, Sydenham, Ontario, Canada
- Provincial Laboratory of Public Health (CA)
- McMaster University (CA)
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2007-08-15
- Volume
- 81
- Issue
- 16
- Pages
- 8692-8706
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC1951379
- OpenAlex
- W2049902839
- Cited by
- 386
- References
- 59
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 31 · 2021: 71 · 2020: 121 · 2019: 5 · 2018: 1 · 2017: 8 · 2016: 7 · 2015: 10 · 2014: 11 · 2013: 10 · 2012: 10
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Genome Canada
- Ontario Genomics
- Ontario Genomics Institute
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS, interferon, type I interferon, interferon-stimulated genes, interferon-alpha, interferon-gamma, chemokines, innate immunity, adaptive immunity, immunopathology, SARS-CoV, spike antibodies, immunoglobulin genes, gene expression signatures, cytokine storm, H5N1 avian influenza, viral pathogenesis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antibodies, Viral, Antibody Formation, Female, Humans, Immunity, Innate, Interferons, Male, Middle Aged, Gene Expression, Cytokines, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genomics, Proteomics, Severe Acute Respiratory Syndrome
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