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Elife. 2019 Apr 9;8. pii: e44360. doi: 10.7554/eLife.44360.

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

Author information

1
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, United States.
2
Yale Center for Genome Analysis Bioinformatics group, Yale University School of Medicine, New Haven, United States.
3
Infectious Diseases Section, Dallas VA Medical Center, Dallas, United States.
4
Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, United States.
5
Ragon Institute of MGH, MIT and Harvard University, Cambridge, United States.
6
Department of Medicine, University of California San Francisco, San Francisco, United States.
7
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, United States.

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.

KEYWORDS:

HIV; ccr2; ccr5; elite controllers; human; infectious disease; microbiology; transcription; viremic controllers; virus

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