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Series GSE144329 Query DataSets for GSE144329
Status Public on Jun 15, 2020
Title A unique viral reservoir landscape associated with durable natural control of HIV-1 infection [ATAC-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Sustained, drug-free control of HIV-1 replication is naturally achieved in less than 0.5% of infected persons (“elite controllers”, ECs), despite the presence of a replication-competent viral reservoir. Such an ability to spontaneously maintain undetectable plasma viremia is a major objective of functional cure efforts, yet the characteristics of proviral reservoirs in ECs remain to be determined. Using single-genome, near full-length next-generation sequencing and chromosomal integration site analysis, we here show that proviral reservoirs of ECs frequently consist of oligoclonal to near monoclonal clusters of identical intact proviral sequences. In contrast to persons treated with long-term antiretroviral therapy, intact proviral species from ECs displayed highly distinct chromosomal integration sites in the human genome and were preferentially located in centromeric satellite DNA or in KRAB-ZNF genes on chromosome 19, both of which are associated with heterochromatin features. Moreover, integration sites of intact proviruses from ECs showed increased distance to host transcriptional start sites and accessible chromatin and were enriched for repressive chromatin marks. These data suggest that a distinct proviral reservoir configuration represents a structural correlate of natural viral control, and that quality rather than quantity of viral reservoirs can be an important distinguishing feature for a functional cure of HIV-1 infection. Moreover, failure to detect intact proviral sequences despite analyzing > 1.5 billion peripheral blood mononuclear cells in one EC raises the possibility that a sterilizing cure of HIV-1 infection, previously only observed following allogeneic hematopoietic stem cell transplantation, may be feasible in rare instances.
 
Overall design We performed RNAseq and ATACseq on 5 subsets of CD4 T cells from Elite controller and ART-treated patient PBMC samples to prolife transcriptome and chromatin accessiblity.
 
Contributor(s) Jiang C, Lian X, Gao C, Sun X, Chevalier J, Einkauf K, Chen S, Blackmer J, Hua S, Rhee B, Peluso M, Hoh R, Bertagnolli L, Sweet S, Varriale J, Laird G, Serrao E, Engelman A, Carrington M, Siliciano R, Siliciano J, Deeks S, Walker B, Lichterfeld M
Citation(s) 32848246, 35026153, 36596305
Submission date Jan 27, 2020
Last update date Feb 02, 2023
Contact name Ce Gao
E-mail(s) CGAO4@MGH.HARVARD.EDU
Organization name Ragon Institute of MGH, MIT and Harvard
Lab Yu/Lichterfeld Labs
Street address 400 Technology Square
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (96)
GSM4285936 ART Patient 01 ATACseq Central memory CD4 T cells (1)
GSM4285937 ART Patient 01 ATACseq Central memory CD4 T cells (2)
GSM4285938 ART Patient 01 ATACseq Effector memory CD4 T cells (1)
This SubSeries is part of SuperSeries:
GSE144334 A unique viral reservoir landscape associated with durable natural control of HIV-1 infection
Relations
BioProject PRJNA603385
SRA SRP245433

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Supplementary file Size Download File type/resource
GSE144329_summits.bed.gz 27.8 Mb (ftp)(http) BED
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Processed data are available on Series record

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