Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members

Elena Gonzalo-Gil, Patrick B. Rapuano, Uchenna Ikediobi, Rebecca Leibowitz, Sameet Mehta, Ayse K. Coskun, J. Zachary Porterfield, Teagan D. Lampkin, Vincent C. Marconi, David Rimland, Bruce D. Walker, Steven Deeks, Richard E. Sutton

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish
Article numbere44360
StatePublished - 2019

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ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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