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Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members
- Source :
- eLife, Vol 8 (2019)
- Publication Year :
- 2019
- Publisher :
- eLife Sciences Publications Ltd, 2019.
-
Abstract
- 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 RNA 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 ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb 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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.fc6ea9035e324f85a1801ebed0225c9a
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.44360