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

doi:10.7554/eLife.44360

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

Microbiology, Immunology, and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English
Article number	e44360
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.44360
State	Published - 2019

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© 2019, eLife Sciences Publications Ltd. All rights reserved.

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.44360

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

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.",

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

year = "2019",

doi = "10.7554/eLife.44360",

language = "English",

volume = "8",

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T1 - Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members

AU - Gonzalo-Gil, Elena

AU - Rapuano, Patrick B.

AU - Ikediobi, Uchenna

AU - Leibowitz, Rebecca

AU - Mehta, Sameet

AU - Coskun, Ayse K.

AU - Porterfield, J. Zachary

AU - Lampkin, Teagan D.

AU - Marconi, Vincent C.

AU - Rimland, David

AU - Walker, Bruce D.

AU - Deeks, Steven

AU - Sutton, Richard E.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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