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| Status |
Public on Jul 23, 2014 |
| Title |
Type I IFN responses in rhesus macaques prevent SIV transmission and slow disease progression |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In acute HIV infection immune activation may provide target cells and drive virus replication, which innate immunity may limit. Thus, the net effects of inflammatory mediators, including type I interferon (IFN-I), are unclear. Here, we block IFN-I signaling during pathogenic acute SIV infection with an IFN-I receptor antagonist. Delayed antiviral gene expression, increased SIV reservoir, increased CD4 T cell depletion and accelerated progression to AIDS and death ensue despite decreased T cell activation. In contrast, IFNα2a treatment initially upregulates antiviral genes and prevents systemic SIV infection after rectal challenge. Antiviral gene expression normalizes, and infection ensues with fewer transmitted/founder variants. Continued IFNα2a treatment causes delayed antiviral gene expression, increased SIV reservoir and increased CCR5+ CD4 T cell loss. Thus, the precise timing of antiviral gene expression has a profound impact on disease course. The benefits of early antiviral activity outweigh the harms of increased immune activation in acute SIV infection.
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| Overall design |
SRA Study accession: SRP034563, BioProject ID:PRJNA231884
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| Contributor(s) |
Sandler NG, Bosinger SE, Estes JD, Zhu RT, Boritz E, Tharp GK, Levin D, Wijeyesinghe S, Makamdop KN, del Prete G, Hill BJ, Modi N, Timmer KJ, Reiss E, Darko S, Contijoch E, Todd JP, Silvestri G, Nason M, Keele BF, Rao S, Langer JA, Lifson JD, Schreiber G, Douek DC |
| Citation(s) |
25043006 |
| BioProject |
PRJNA231884 |
| Submission date |
Dec 27, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Gregory K Tharp |
| E-mail(s) |
gktharp@emory.edu
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| Phone |
404-727-7797
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| Organization name |
Yerkes National Primate Research Center
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| Department |
Developmental and Cognitive Neuroscience
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| Lab |
Genomics Core
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| Street address |
954 Gatewood Dr
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30329-4208 |
| Country |
USA |
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| Platforms (1) |
| GPL14954 |
Illumina HiSeq 2000 (Macaca mulatta) |
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| Samples (203)
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| Relations |
| SRA |
SRP034563 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE53690_Acute_LN-CD4_FPKM_exprs.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE53690_Acute_PBMC_Uninfected_FPKM_exprs.txt.gz |
7.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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