Work

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

Year: 2019

Type: article

Study design: Observational Study

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.

Source: eLife

DOI: 10.7554/elife.44360

Authors: 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

Institutions: Yale University, Dallas VA Medical Center, Emory University, Atlanta VA Medical Center, Harvard University, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, University of California, San Francisco

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500

Funders: Bill and Melinda Gates Foundation, amfAR, The Foundation for AIDS Research, Delaney AIDS Research Enterprise, Emory University, Harvard University, Harvard University Center for AIDS Research, National Institutes of Health, School of Medicine, Emory University, Center for AIDS Research, University of Washington, University of California, San Francisco, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences

Awards: G1203476693, G1245695584, G1255407591, G150015232, G1575283533, G1722716446, G1869768155, G2428225874, G2675028044, G2839755957, G3181090803, DARE: Delaney AIDS Research Enterprise to find a cure., 2/6 COMpAAAS U01: Observation Study, G3423487890, G345173699, G3917235369, G4166928756, G4228988029, Alcohol Associated Outcomes Among HIV+/- Aging Veterans, High Performance Computing Instrumentation for the Yale Center for Genome Analysi, G5934524914, G6113675784, G6444951560, Host Genetic Control of HIV, G6655413242, G6759634997, G7785852513, G7798477230, G864826021, G9000078127, G9000129761, G9000271296, CFAR Network of Integrated Clinical Systems (CNICS), Center for AIDS Research at Emory University, UCSF-Bay Area Center for AIDS Research, Harvard University Center for AIDS Research, Yale Clinical and Translational Science Award, Training in Investigative Infectious Diseases

OpenAlex ID: W2937629316

FWCI: 1.794

Cites: 56

Cited by: 25

Related to: 10