Cited by 392interferon and immune responsesSARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studies

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Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome

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Cameron, Mark J., Ran, Longsi, Xu, Luoling, Danesh, Ali, Bermejo-Martin, Jesus F., Cameron, Cheryl M., Muller, Matthew P., Gold, Wayne L., Richardson, Susan E., Poutanen, Susan M., Willey, Barbara M., DeVries, Mark E., Fang, Yuan, Seneviratne, Charit, Bosinger, Steven E., Persad, Desmond, Wilkinson, Peter, Greller, Larry D., Somogyi, Roland, Humar, Atul, Keshavjee, Shaf, Louie, Marie, Loeb, Mark B., Brunton, James, McGeer, Allison J., the Canadian SARS Research Network, Kelvin, David J.·2007·Journal of Virology

DOI 10.1128/jvi.00527-07PMC PMC1951379

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Abstract

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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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: Cameron, Mark J.
Xu, Luoling
Danesh, Ali
Cameron, Cheryl M.
Muller, Matthew P.
Gold, Wayne L.
Richardson, Susan E.
Poutanen, Susan M.
Bosinger, Steven E.
Wilkinson, Peter
Humar, Atul
Keshavjee, Shaf
Loeb, Mark B.
McGeer, Allison J.
Kelvin, David J.
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
DOI: 10.1128/jvi.00527-07
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome

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