Channappanavar, Rudragouda and Fehr, Anthony R. and Zheng, Jian and Wohlford-Lenane, Christine and Abrahante, Juan E. and Mack, Matthias and Sompallae, Ramakrishna and McCray, Paul B. and Meyerholz, David K. and Perlman, Stanley (2019) IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. JOURNAL OF CLINICAL INVESTIGATION, 129 (9). pp. 3625-3639. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)Abstract
Type 1 IFNs (IFN-I) generally protect mammalian hosts from virus infections, but in some cases, IFN-I is pathogenic. Because IFN-I is protective, it is commonly used to treat virus infections for which no specific approved drug or vaccine is available. The Middle East respiratory syndrome-coronavirus (MERS-CoV) is such an infection, yet little is known about the role of IFN-I in this setting. Here, we show that IFN-I signaling is protective during MERS-CoV infection. Blocking IFN-I signaling resulted in delayed virus clearance, enhanced neutrophil infiltration, and impaired MERS-CoV-specific T cell responses. Notably, IFN-I administration within 1 day after infection (before virus titers peak) protected mice from lethal infection, despite a decrease in IFN-stimulated gene (ISG) and inflammatory cytokine gene expression. In contrast, delayed IFN-beta treatment failed to effectively inhibit virus replication; increased infiltration and activation of monocytes, macrophages. and neutrophils in the lungs; and enhanced proinflammatory cytokine expression, resulting in fatal pneumonia in an otherwise sublethal infection. Together, these results suggest that the relative timing of the IFN-I response and maximal virus replication is key in determining outcomes, at least in infected mice. By extension, IFN-alpha beta or combination therapy may need to be used cautiously to treat viral infections in clinical settings.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RESPIRATORY SYNDROME CORONAVIRUS; MOUSE HEPATITIS-VIRUS; T-CELL RESPONSES; CLONAL EXPANSION; IMMUNE-RESPONSES; LUNG PATHOLOGY; INTERFERON; SARS; MACROPHAGES; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 09:49 |
| Last Modified: | 06 Apr 2020 09:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26278 |
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