Table 1.

Studies of HIV-1 integration sites (IS) in vitro and in vivo

Type of study	Cell type	No. of IS	Location	Main observations	Reference
In vitro infection of T cell lines
T cell line	Jurkat	7171	GDR	IS within gene dense regions	[44]
T cell line	J-Lat A1	130	NP	Inducible provirus in gene deserts	[45]
T cell line	Jurkat	40,569	TAHM	IS within genes active in mitosis, life cycle, and RNA metabolism	[25]
T cell line	Jurkat	971	α-Repeat, GD	IS in low expression genes	[76]
T cell line	Hu primary cells and cell lines	10	TSS	Latency in IS in reverse orientation compared to host gene	[77]
Cell line	Hu primary cells and cell lines	3127 MLV, HIV, ASLV	TU	75 % of integration into tissue-specific active genes	[20]
T cell line	Jurkat	8	Heterochromatin	IS within genes with low level of transcription	[23]
Cell line	HeLa and H9	903 MLV 379 HIV	TU	TSS favored by MLV not by HIV	[30]
T cell line	SupT1	59	TU	IS within genes with high gene density and GC-rich regions	[22]
T cell line	SupT1	524	GDR	IS within introns and alpha satellite	[21]
Cell lines	Jurkat, HeLa, 293T, SW13, CEM, and A301	34	NR	Specific IS determine the expression of latent proviruses	[24]
T cell line	SupT1	61	TU	IS not near centromere	[46]
In vitro infection of primary T cells
Primary cells	Activated and rCD4 T cells infected by spinoculation	6184 inducible 6252 express	Away from CpG, α-repeat heterochromatin	Latency in low expression genes. EGFP HIV similar in resting or activated. No consistent IS across models	[66••]
Primary cells	Activated and rCD4 T Cells	NR	α-Repeat, GC region	Integration site selection promotes viral expression	[64•]
Primary cells	Bcl2_Transduced CD4 T Cells	224 Ac 216 Ch 493 lat	TU and HAG	Integration sites in same orientation. Transcriptional interference lead to latency	[19•]
Primary cells	Activated and rCD4 T cells	451	TSS and GC regions	IS were selective	[53]
Primary cells	Activated and rCD4 T cells	2661	TU and AG	IS were similar in activated vs resting CD4 T cells	[65]
Primary cells	PBMC and monocytes	754	TU	IS were different in macrophages compared to dividing PBMC	[54]
Integration sites in vivo and patient-derived T cells
Patients on cART	PBMC, CD4 T cells	1632	Growth and cell regulation	Clonal expansion of HIV-infected cells, multiple IS in BACH2 and MKL2	[68••]
Patients on cART	Unsorted PBMC	534	Proliferation and survival	Multiple insertion in 12 cancer-related genes including BACH2	[69••]
Patients on cART	PBMC, rCD4 T cells	594	TU	Clonally expanded cells, multiple IS in SMC5 and BACH2 genes	[71•]
Patients on cART	rCD4 T cells	62	TU	92.9 % of noninduced provirus found in active transcribed units	[67••]
Patients on cART	rCD4 T cells	457	TU	Selective integration in BACH2	[72]
Untreated patients	PBMC, tissues	43	GDR	Viral integration in coding genes	[78]
In vivo	CD34+ from rhesus macaque	432 MLV 328 SIV	TU, SIV, TSS, MLV	Site around TSS favored by MLV, but IS within the TU in SIV	[29]
Patients on cART	rCD4 T cells	74	TU	IS in actively transcribed genes	[52]

GDR gene dense region, NP nuclear periphery, TAHM transcriptional associated histone modification, GD gene dessert, TSS transcription start site, TU transcriptional unit, NR not reported, rCD4 resting CD4 cells, HAG highly active genes, AG active gene, PBMC peripheral blood mononuclear cells, MLV murine leukemia virus, ASLV avian sarcoma-leukosis virus, Ac acute, Ch chronic, lat latent, pat patient