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| Status |
Public on Mar 09, 2020 |
| Title |
Nef-mediated downmodulation of CD3 dampens immune activation and is critical for maintenance of high virus loads in SIV-infected macaques |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The inability of Nef to downmodulate the T cell receptor CD3 distinguishes HIV-1 from most other primate lentiviruses and may contribute to its high virulence. However, the role of this Nef function in viral immune evasion and pathogenicity remained speculative. Here, we selectively disrupted this Nef activity in SIVmac239 and analyzed the consequences for the virological, immunological and clinical outcome of infection in rhesus macaques. The inability to downmodulate CD3 did not affect viral replication during acute infection but was associated with increased immune activation and antiviral gene expression. Thus, Nef-mediated downmodulation of CD3 dampens the inflammatory response to SIV infection and is critical for viral immune evasion.
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| Overall design |
Twelve young adult rhesus macaques were distributed to two groups with six monkeys each. Animals in the first group (n=6) were inoculated intravenously with infectious doses of CD3ko-Nef SIVmac239 (CD3ko), SIVmac239 containing 2 point mutations in Nef. The animals of the other group (n=6) received SIVmac239 wild type (wt) at the same dose and by the same route as for the mutant virus.
Blood samples (PBMC) were collected and peripheral lymph nodes (LN) were surgically removed before and post-infection.
The samples were collected in two sets of experiments, A and B. Set A consists of PBMC and LN samples from wt (n=3) and CD3ko (n=3) infected animals at 2 weeks post-infection. For Set A, PBMC samples were also collected from uninfected control animals (n=10). Set B consists of PBMC and LN samples from wt (n=3) and CD3ko (n=3) infected animals at both pre- and post-infection time-points.
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| Contributor(s) |
Joas S, Sauermann U, Neumann B, Klippert A, Stolte-Leeb N, Heigele A, Schmökel J, Tharp GK, Nelson SA, Gupta PM, Bosinger S, Parodi L, Giavedoni L, Silvestri G, Sauter D, Stahl-Hennig C, Kirchhoff F |
| Citation(s) |
32075764 |
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| Submission date |
Dec 08, 2019 |
| Last update date |
Apr 10, 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 (40)
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| Relations |
| BioProject |
PRJNA594204 |
| SRA |
SRP235121 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141626_ExpAandB_Kirchhoff_DESeq2_NormCounts_LN.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE141626_ExpAandB_Kirchhoff_DESeq2_NormCounts_PBMC.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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