Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.44360
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Funding
- National Institutes of Health [P30AI050409, U01 AA020790]
- Bill and Melinda Gates Foundation
- Harvard University Center for AIDS Research [P30 AI060354]
- Collaboration for AIDS Vaccine Discovery (CAVD)
- UCSF/Gladstone Institute of Virology and Immunology [P30 AI027763]
- CFAR Network of Integrated Systems [R24 AI067039]
- Delaney AIDS Research Enterprise DARE [AI096109, A127966]
- amfAR Institute for HIV cure research [109301]
- National Institute on Drug Abuse [DP1DA036463]
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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 downregulated, over a region of similar to 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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