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| Status |
Public on Feb 03, 2017 |
| Title |
Immune Escape via A Transient Gene Expression Program Enables Productive Replication of A Latent Pathogen |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
How type I / II interferons (IFNs) prevent periodic re-emergence of latent pathogens in tissues of diverse cell-types remains unknown. Using homogenous neuron cultures latently-infected with herpes simplex virus (HSV), we show that extrinsic type I or II IFN act directly on neurons to induce unique gene expression signatures and inhibit the reactivation-specific burst of viral genome-wide transcription called Phase I. Surprisingly, IFNs suppressed reactivation only during a limited period early in Phase I preceding productive virus growth. Sensitivity to type II IFN was selectively lost if viral ICP0, which normally accumulates later in Phase I, was expressed prior to reactivation. Thus, IFNs suppress reactivation by preventing initial expression of latent genomes but are ineffective once Phase I viral proteins accumulate and limit IFN action. This demonstrates that inducible reactivation from latency is only transiently sensitive to IFNs. Moreover, it illustrates how latent pathogens escape host immune control to periodically replicate by rapidly deploying an interferon-resistant state.
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| Overall design |
Superior cervical ganglia (SCG) neuron cultures harboring reactivating HSV-1 treated with IFNb or IFNg. Neurons were harvested for RNA 20h after reactivation (in the presence or absence of IFN) for RNA-seq. Libraries were generated following Illumina Truseq Ribo-Zero protocol.
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| Contributor(s) |
Kobayashi M, Mohr I, Darnell RB |
| Citation(s) |
28147283 |
| Submission date |
Dec 01, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Mariko Kobayashi |
| E-mail(s) |
mkobayashi@rockefeller.edu
|
| Organization name |
Rockefeller University
|
| Department |
Molecular Neuro-Oncology
|
| Lab |
Robert B. Darnell
|
| Street address |
1230 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA355653 |
| SRA |
SRP094421 |
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