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| Status |
Public on Dec 06, 2023 |
| Title |
Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates viral immune sensing, and induces cell-cycle arrest in cell culture. However, its impact in vivo is controversial. Here, we show that deletion of vpr is associated with delayed viral replication kinetics, rapid innate immune activation, development and maintenance of strong B cell responses, and generation of higher avidity p27 Gag antibodies in rhesus macaques. All wild-type SIVmac239 infected animals maintained high viral loads and five of six developed fatal immunodeficiency during ~80 weeks of follow-up. Lack of Vpr was associated with better preservation of CD4+ T cells, lower viral loads and an attenuated clinical course of infection in most animals. Our results demonstrate that Vpr contributes to efficient viral immune evasion and the full pathogenic potential of SIVmac in vivo. Inhibition of Vpr may improve humoral immune control of viral replication.
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| Overall design |
Six rhesus macaques were infected with a mutant SIVmac239 construct containing a large deletion of 101 nucleotides eliminating the vpr gene (Δvpr), and six rhesus macaques were infected with wild type (wt) SIVmac239, and 10 rhesus macaques were uninfected. Blood samples (PBMC) were collected in two sets of experiments, A and B. Set A consists of wt (n=3) and Δvpr (n=3) infected animals at 2 and 24 weeks post-infection. For Set A, PBMC samples were also collected from uninfected control animals (n=10). Set B consists of blood samples from wt (n=3) and Δvpr (n=3) infected animals at both pre- (4 and 8 weeks) and post-infection (2 and 24 weeks) time-points.
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| Contributor(s) |
Laliberté A, Bozzo CP, Stahl-Hennig C, Hunzinger V, Joas S, Sauermann U, Roshani B, Klippert A, Daskalaki M, Mätz-Rensing K, Stolte-Leeb N, Daskalaki M, Tharp GK, Fuchs D, Gupta PM, Silvestri G, Nelson S, Parodi L, Giavedoni L, Bosinger S, Sparrer KM, Kirchhoff F |
| Citation(s) |
38025783 |
| Submission date |
Apr 10, 2023 |
| Last update date |
Dec 06, 2023 |
| 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) |
| GPL23804 |
Illumina HiSeq 3000 (Macaca mulatta) |
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| Samples (46)
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| Relations |
| BioProject |
PRJNA953997 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229310_ExpAandB_Kirchhoff_Vpr_RawCounts.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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