Channappanavar, Rudragouda and Fehr, Anthony R. and Vijay, Rahul and Mack, Matthias and Zhao, Jincun and Meyerholz, David K. and Perlman, Stanley (2016) Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. CELL HOST & MICROBE, 19 (2). pp. 181-193. ISSN 1931-3128, 1934-6069
Full text not available from this repository. (Request a copy)Abstract
Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (severe acute respiratory syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak, but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocyte-macrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage, and impaired virus-specific T cell responses. Genetic ablation of the IFN-ab receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS INFECTION; T-CELL RESPONSES; PERSISTENT LCMV INFECTION; DENDRITIC CELLS; VIRUS-INFECTION; INFLUENZA INFECTION; IMMUNE-RESPONSES; LUNG PATHOLOGY; PATHOGENESIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 11:37 |
| Last Modified: | 12 Mar 2019 11:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2406 |
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