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| Status |
Public on Apr 08, 2019 |
| Title |
Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers (RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
HIV+ Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4+ T cells with resistance specific to R5-tropic HIV, reversed after introduction of CCR5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4+ T cells of these EC/VCs had lower CCR2 and CCR5 mRNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of CCR2 and CCR5, despite having more accessible chromatin by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq). Other nearby genes were also down-regulated, over a region of ~500kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with CCR2/CCR5 down-regulation, suggesting that the phenotype is heritable.
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| Overall design |
RNA-seq was performed to identify up- or down-regulated genes associated with in vitro resistance to R5-tropic viruses in activated CD4+ T cells from HIV+ Elite Controllers and family members
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| Contributor(s) |
Gonzalo-Gil E, Rapuano PB, Ikediobi U, Leibowitz R, Mehta S, Coskun AK, Porterfield JZ, Lampkin TD, Marconi VC, Rimland D, Walker BD, Deeks S, Sutton RE |
| Citation(s) |
30964004 |
| |
| Submission date |
Nov 08, 2018 |
| Last update date |
Apr 17, 2019 |
| Contact name |
Elena Gonzalo Gil |
| E-mail(s) |
elena.gonzalogil@yale.edu
|
| Phone |
2039994272
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| Organization name |
Yale University School of Medicine
|
| Street address |
25 York street
|
| City |
New Haven |
| State/province |
Connecticut |
| ZIP/Postal code |
06510 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE122323 |
Transcriptional Down-regulation of CCR5 in a Subset of HIV+ Controllers |
|
| Relations |
| BioProject |
PRJNA504631 |
| SRA |
SRP168232 |
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