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 | |
| State | Published - 2019 |
Bibliographical note
Funding Information:National Institutes of Health P30AI050409 Vincent C Marconi National Institutes of Health U01 AA020790 Vincent C Marconi Bill and Melinda Gates Foun- dation Bruce D Walker Harvard University Center for AIDS Research P30 AI060354 Bruce D Walker The Collaboration for AIDS Vaccine Discovery (CAVD) Bruce D Walker UCSF/Gladstone Institute of Virology and Immunology P30 AI027763 Steven Deeks CFAR Network of Integrated Systems R24 AI067039 Steven Deeks Delaney AIDS Research Enter- prise DARE; AI096109,A127966 Steven Deeks The amfAR Institute for HIV cure research amfAR 109301 Steven Deeks National Institute on Drug Abuse DP1DA036463 Richard E Sutton The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Funding Information:
We would like to thank the clinical coordinators at Emory University School of Medicine, especially Rincy Varughese, Cameron England, Rachel Safeek, Ramona Rai, and Clayton Carruth. The SCOPE cohort was supported the UCSF/Gladstone Institute of Virology and Immunology CFAR (P30 AI027763) and CFAR Network of Integrated Systems (R24 AI067039). Additional support was provided by the Delaney AIDS Research Enterprise (DARE; AI096109, A127966) and amfAR Institute for HIV Cure Research (amfAR 109301). This work was supported in part by the Bill and Melinda Gates Foundation and the Collaboration for AIDS Vaccine Discovery (BDW) and the Harvard University Center for AIDS Research grant P30 AI060354 (BDW), supported by the following NIH co-funding and participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. This work was also supported by the following NIH grants: P30AI050409, U01 AA020790, U10 AA013566, and DP1DA036463. We thank Dr. Ned Landau of NYU Medical Center for kind gift plasmids. RES is a NIDA Avant Garde awardee.
Publisher Copyright:
© 2019, eLife Sciences Publications Ltd. All rights reserved.
ASJC Scopus subject areas
- Neuroscience (all)
- Biochemistry, Genetics and Molecular Biology (all)
- Immunology and Microbiology (all)
