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| Status |
Public on Feb 05, 2019 |
| Title |
HIV-1 Vpu exerts broad immunosuppressive effects by inhibiting NF-κB-dependent gene expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Using an unbiased RNA sequencing approach of primary CD4+ T cells infected with three wild type primary HIV-1 isolates and selective mutants thereof, Langer et al. show that the HIV-1 accessory protein Vpu exerts broad immunosuppressive effects, inhibiting the induction of innate and adaptive immune responses. Transcription factor network analyses reveal that Vpu suppresses the expression of NF‑κB rather than IRF3 target genes. As a result, Vpu impairs the production of pro-inflammatory cytokines such as IFNβ, CXCL10 and IL-6.
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| Overall design |
Human CD4+ T cells, isolated from 4 independent healthy donors, A1, X, Y and Z (corresponding to A, B, C and D in the publication), were infected with equal amounts of three different HIV-1 primary isolates, two of them being clade B viruses (HIV-1 CH077 and HIV-1 STCO1) and one of them being a clade C virus (HIV-1 CH293). In addition, CD4+ T cells were infected with mutant viruses of the aforementioned primary isolates. Specific mutations were introduced in these viruses to either abrogate Vpu expression ("vpu stop"), or selectively abrogate Vpu-mediated counteraction of the antiviral protein tetherin ("A20L/A24L" or "A15L/A19L") or NF-kB inhibition ("R50K" or "R45K"). Global RNA of infected cells was collected 72 hours post infection and processed for RNA-Seq analysis.
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| Contributor(s) |
Langer S, Hammer C, De Jesus PD, Herbert KM, Pache L, Chanda SK, Fellay J, Sauter D |
| Citation(s) |
30717826, 33021676 |
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https://doi.org/10.7554/eLife.41930
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| Submission date |
Jul 25, 2018 |
| Last update date |
Nov 16, 2020 |
| Contact name |
Lars Pache |
| Organization name |
Sanford Burnham Prebys Medical Discovery Institute
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| Street address |
10901 N Torrey Pines Rd
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| City |
La Jolla |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (52)
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| Relations |
| BioProject |
PRJNA482835 |
| SRA |
SRP155217 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE117655_RAW.tar |
112.9 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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