Accession	GSE144329
Status	2020/6/15
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.
Samples	GSM ID Sample info Characteristics Description GSM4285959 ART Patient 03 ATACseq Naive CD4 T cells (1) patient:ART Patient 03; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285960 ART Patient 03 ATACseq Naive CD4 T cells (2) patient:ART Patient 03; tissue:peripheral blood; replicate:2; cell type:Naive CD4 T cells - GSM4285961 ART Patient 03 ATACseq TEMRA CD4 T cells (1) patient:ART Patient 03; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285962 ART Patient 03 ATACseq TEMRA CD4 T cells (2) patient:ART Patient 03; tissue:peripheral blood; replicate:2; cell type:TEMRA CD4 T cells - GSM4285963 ART Patient 03 ATACseq Total CD4 T cells (1) patient:ART Patient 03; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285964 ART Patient 03 ATACseq Total CD4 T cells (2) patient:ART Patient 03; tissue:peripheral blood; replicate:2; cell type:Total CD4 T cells - GSM4285965 EC Patient 01 ATACseq Central memory CD4 T cells (1) patient:EC Patient 01; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285966 EC Patient 01 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 01; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285967 EC Patient 01 ATACseq Naive CD4 T cells (1) patient:EC Patient 01; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285968 EC Patient 01 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 01; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285969 EC Patient 01 ATACseq Total CD4 T cells (1) patient:EC Patient 01; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285936 ART Patient 01 ATACseq Central memory CD4 T cells (1) patient:ART Patient 01; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285937 ART Patient 01 ATACseq Central memory CD4 T cells (2) patient:ART Patient 01; tissue:peripheral blood; replicate:2; cell type:Central memory CD4 T cells - GSM4285938 ART Patient 01 ATACseq Effector memory CD4 T cells (1) patient:ART Patient 01; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285939 ART Patient 01 ATACseq Effector memory CD4 T cells (2) patient:ART Patient 01; tissue:peripheral blood; replicate:2; cell type:Effector memory CD4 T cells - GSM4285940 ART Patient 01 ATACseq Naive CD4 T cells (1) patient:ART Patient 01; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285941 ART Patient 01 ATACseq Naive CD4 T cells (2) patient:ART Patient 01; tissue:peripheral blood; replicate:2; cell type:Naive CD4 T cells - GSM4285970 EC Patient 02 ATACseq Central memory CD4 T cells (1) patient:EC Patient 02; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285942 ART Patient 01 ATACseq TEMRA CD4 T cells (1) patient:ART Patient 01; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285943 ART Patient 01 ATACseq TEMRA CD4 T cells (2) patient:ART Patient 01; tissue:peripheral blood; replicate:2; cell type:TEMRA CD4 T cells - GSM4285971 EC Patient 02 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 02; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285944 ART Patient 01 ATACseq Total CD4 T cells (1) patient:ART Patient 01; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285972 EC Patient 02 ATACseq Naive CD4 T cells (1) patient:EC Patient 02; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285973 EC Patient 02 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 02; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285945 ART Patient 01 ATACseq Total CD4 T cells (2) patient:ART Patient 01; tissue:peripheral blood; replicate:2; cell type:Total CD4 T cells - GSM4285974 EC Patient 02 ATACseq Total CD4 T cells (1) patient:EC Patient 02; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285946 ART Patient 02 ATACseq Central memory CD4 T cells (1) patient:ART Patient 02; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285975 EC Patient 03 ATACseq Central memory CD4 T cells (1) patient:EC Patient 03; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285947 ART Patient 02 ATACseq Central memory CD4 T cells (2) patient:ART Patient 02; tissue:peripheral blood; replicate:2; cell type:Central memory CD4 T cells - GSM4285976 EC Patient 03 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 03; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285948 ART Patient 02 ATACseq Effector memory CD4 T cells (1) patient:ART Patient 02; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285996 EC Patient 07 ATACseq Central memory CD4 T cells (2) patient:EC Patient 07; tissue:peripheral blood; replicate:2; cell type:Central memory CD4 T cells - GSM4286031 EC Patient 12 ATACseq Total CD4 T cells (1) patient:EC Patient 12; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285997 EC Patient 07 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 07; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285998 EC Patient 07 ATACseq Effector memory CD4 T cells (2) patient:EC Patient 07; tissue:peripheral blood; replicate:2; cell type:Effector memory CD4 T cells - GSM4285999 EC Patient 07 ATACseq Naive CD4 T cells (1) patient:EC Patient 07; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286000 EC Patient 07 ATACseq Naive CD4 T cells (2) patient:EC Patient 07; tissue:peripheral blood; replicate:2; cell type:Naive CD4 T cells - GSM4286001 EC Patient 07 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 07; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286002 EC Patient 07 ATACseq Total CD4 T cells (1) patient:EC Patient 07; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4286003 EC Patient 07 ATACseq Total CD4 T cells (2) patient:EC Patient 07; tissue:peripheral blood; replicate:2; cell type:Total CD4 T cells - GSM4286004 EC Patient 08 ATACseq Central memory CD4 T cells (1) patient:EC Patient 08; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285949 ART Patient 02 ATACseq Effector memory CD4 T cells (2) patient:ART Patient 02; tissue:peripheral blood; replicate:2; cell type:Effector memory CD4 T cells - GSM4285977 EC Patient 03 ATACseq Naive CD4 T cells (1) patient:EC Patient 03; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286005 EC Patient 08 ATACseq Central memory CD4 T cells (2) patient:EC Patient 08; tissue:peripheral blood; replicate:2; cell type:Central memory CD4 T cells - GSM4286006 EC Patient 08 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 08; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4286007 EC Patient 08 ATACseq Effector memory CD4 T cells (2) patient:EC Patient 08; tissue:peripheral blood; replicate:2; cell type:Effector memory CD4 T cells - GSM4286008 EC Patient 08 ATACseq Naive CD4 T cells (1) patient:EC Patient 08; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286009 EC Patient 08 ATACseq Naive CD4 T cells (2) patient:EC Patient 08; tissue:peripheral blood; replicate:2; cell type:Naive CD4 T cells - GSM4286010 EC Patient 08 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 08; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286011 EC Patient 08 ATACseq Total CD4 T cells (1) patient:EC Patient 08; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285950 ART Patient 02 ATACseq Naive CD4 T cells (1) patient:ART Patient 02; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286012 EC Patient 09 ATACseq Central memory CD4 T cells (1) patient:EC Patient 09; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4286013 EC Patient 09 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 09; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4286014 EC Patient 09 ATACseq Naive CD4 T cells (1) patient:EC Patient 09; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286015 EC Patient 09 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 09; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286016 EC Patient 09 ATACseq Total CD4 T cells (1) patient:EC Patient 09; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4286017 EC Patient 10 ATACseq Central memory CD4 T cells (1) patient:EC Patient 10; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4286018 EC Patient 10 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 10; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4286019 EC Patient 10 ATACseq Naive CD4 T cells (1) patient:EC Patient 10; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286020 EC Patient 10 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 10; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286021 EC Patient 10 ATACseq Total CD4 T cells (1) patient:EC Patient 10; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4286022 EC Patient 11 ATACseq Central memory CD4 T cells (1) patient:EC Patient 11; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4286023 EC Patient 11 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 11; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4286024 EC Patient 11 ATACseq Naive CD4 T cells (1) patient:EC Patient 11; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285978 EC Patient 03 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 03; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286025 EC Patient 11 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 11; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286026 EC Patient 11 ATACseq Total CD4 T cells (1) patient:EC Patient 11; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285951 ART Patient 02 ATACseq Naive CD4 T cells (2) patient:ART Patient 02; tissue:peripheral blood; replicate:2; cell type:Naive CD4 T cells - GSM4285979 EC Patient 03 ATACseq Total CD4 T cells (1) patient:EC Patient 03; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285952 ART Patient 02 ATACseq TEMRA CD4 T cells (1) patient:ART Patient 02; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285980 EC Patient 04 ATACseq Central memory CD4 T cells (1) patient:EC Patient 04; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285953 ART Patient 02 ATACseq Total CD4 T cells (1) patient:ART Patient 02; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285981 EC Patient 04 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 04; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285954 ART Patient 02 ATACseq Total CD4 T cells (2) patient:ART Patient 02; tissue:peripheral blood; replicate:2; cell type:Total CD4 T cells - GSM4285982 EC Patient 04 ATACseq Naive CD4 T cells (1) patient:EC Patient 04; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285955 ART Patient 03 ATACseq Central memory CD4 T cells (1) patient:ART Patient 03; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285983 EC Patient 04 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 04; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285956 ART Patient 03 ATACseq Central memory CD4 T cells (2) patient:ART Patient 03; tissue:peripheral blood; replicate:2; cell type:Central memory CD4 T cells - GSM4285984 EC Patient 04 ATACseq Total CD4 T cells (1) patient:EC Patient 04; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285957 ART Patient 03 ATACseq Effector memory CD4 T cells (1) patient:ART Patient 03; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285985 EC Patient 05 ATACseq Central memory CD4 T cells (1) patient:EC Patient 05; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285958 ART Patient 03 ATACseq Effector memory CD4 T cells (2) patient:ART Patient 03; tissue:peripheral blood; replicate:2; cell type:Effector memory CD4 T cells - GSM4285986 EC Patient 05 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 05; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285987 EC Patient 05 ATACseq Naive CD4 T cells (1) patient:EC Patient 05; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4285988 EC Patient 05 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 05; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4285989 EC Patient 05 ATACseq Total CD4 T cells (1) patient:EC Patient 05; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285990 EC Patient 06 ATACseq Central memory CD4 T cells (1) patient:EC Patient 06; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285991 EC Patient 06 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 06; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285992 EC Patient 06 ATACseq Naive CD4 T cells (1) patient:EC Patient 06; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286027 EC Patient 12 ATACseq Central memory CD4 T cells (1) patient:EC Patient 12; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4285993 EC Patient 06 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 06; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells - GSM4286028 EC Patient 12 ATACseq Effector memory CD4 T cells (1) patient:EC Patient 12; tissue:peripheral blood; replicate:1; cell type:Effector memory CD4 T cells - GSM4285994 EC Patient 06 ATACseq Total CD4 T cells (1) patient:EC Patient 06; tissue:peripheral blood; replicate:1; cell type:Total CD4 T cells - GSM4285995 EC Patient 07 ATACseq Central memory CD4 T cells (1) patient:EC Patient 07; tissue:peripheral blood; replicate:1; cell type:Central memory CD4 T cells - GSM4286029 EC Patient 12 ATACseq Naive CD4 T cells (1) patient:EC Patient 12; tissue:peripheral blood; replicate:1; cell type:Naive CD4 T cells - GSM4286030 EC Patient 12 ATACseq TEMRA CD4 T cells (1) patient:EC Patient 12; tissue:peripheral blood; replicate:1; cell type:TEMRA CD4 T cells -
Platform	GPL21697  : NextSeq 550 (Homo sapiens)
Literature	32848246  35026153  36596305
Download	Download Genome Binding/Occupancy Profiling Analysis Data