|
| Status |
Public on May 30, 2019 |
| Title |
Relative timing of type I interferon response and virus replication determines disease outcome during MERS-CoV infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Type 1 interferons (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 post infection (before virus titers peak) protected mice from lethal infection, despite a decrease in ISG (interferon stimulated gene) and inflammatory cytokine gene expression. In contrast, delayed IFN-I treatment failed to effectively inhibit virus replication, increased infiltration and activation of monocyte-macrophages and neutrophils into the lungs and enhanced pro-inflammatory cytokine expression, resulting in fatal pneumonia in an otherwise sub-lethal 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-I or combination therapy may need to be used cautiously to treat virus infections in clinical settings.
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| |
|
| Overall design |
Examination of gene expression in early and late IFN treated lungs after MERS-CoV infection.
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| |
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| Contributor(s) |
Perlman S, Channappanavar R |
| Citation(s) |
31355779 |
| Submission date |
May 29, 2019 |
| Last update date |
Aug 29, 2019 |
| Contact name |
Stanley Perlman |
| E-mail(s) |
stanley-perlman@uiowa.edu
|
| Phone |
3193358549
|
| Organization name |
University of Iowa
|
| Street address |
Dept. Microbiology, BSB 3-712, 51 Newton Road
|
| City |
Iowa City |
| State/province |
Iowa |
| ZIP/Postal code |
52242 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (16)
|
| GSM3831224 |
MERS-CoV-infected-untreated-sacrifice-3dpi [1C1] |
| GSM3831225 |
MERS-CoV-infected-untreated-sacrifice-3dpi [1C2] |
| GSM3831226 |
MERS-CoV-infected-untreated-sacrifice-3dpi [1C3] |
| GSM3831227 |
MERS-CoV-infected-untreated-sacrifice-3dpi [1C4] |
| GSM3831228 |
MERS-CoV-infected-rIFN-treated-1dpi-sacrifice-3dpi [1T1] |
| GSM3831229 |
MERS-CoV-infected-rIFN-treated-1dpi-sacrifice-3dpi [1T2] |
| GSM3831230 |
MERS-CoV-infected-rIFN-treated-1dpi-sacrifice-3dpi [1T3] |
| GSM3831231 |
MERS-CoV-infected-rIFN-treated-1dpi-sacrifice-3dpi [1T4] |
| GSM3831232 |
MERS-CoV-infected-untreated-sacrifice-4dpi [2C1] |
| GSM3831233 |
MERS-CoV-infected-untreated-sacrifice-4dpi [2C2] |
| GSM3831234 |
MERS-CoV-infected-untreated-sacrifice-4dpi [2C3] |
| GSM3831235 |
MERS-CoV-infected-untreated-sacrifice-4dpi [2C4] |
| GSM3831236 |
MERS-CoV-infected-rIFN-treated-2dpi-sacrifice-4dpi [2T1] |
| GSM3831237 |
MERS-CoV-infected-rIFN-treated-2dpi-sacrifice-4dpi [2T2] |
| GSM3831238 |
MERS-CoV-infected-rIFN-treated-2dpi-sacrifice-4dpi [2T3] |
| GSM3831239 |
MERS-CoV-infected-rIFN-treated-2dpi-sacrifice-4dpi [2T4] |
|
| Relations |
| BioProject |
PRJNA545350 |
| SRA |
SRP199796 |
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