HIV VIS Detail Information

> This page shows VIS [4006962] detail information, including site information (chromosome, GRCh38 location, disease, sample, etc) and literature information.

Site Information

DVID	4006962
VISID	TVIS30000089
Chromosome	chr20
GRCh38 Location	32399018
Disease	HIV Infections Acquired Immunodeficiency Syndrome
Sample	PBMC
Virus Reference Genome	K03455.1
Target Gene	ASXL1

Literature Information

PubMed PMID	30688658
Year	2019 Mar 1;129(3):988-998
Journal	The Journal of clinical investigation
Title	Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy.
Author	Einkauf KB,Lee GQ,Gao C,Sharaf R,Sun X,Hua S,Chen SM,Jiang C,Lian X,Chowdhury FZ,Rosenberg ES,Chun TW,Li JZ,Yu XG,Lichterfeld M
Evidence	Chromosomal integration of genome-intact HIV-1 sequences into the host genome creates a reservoir of virally infected cells that persists throughout life, necessitating indefinite antiretroviral suppression therapy. During effective antiviral treatment, the majority of these proviruses remain transcriptionally silent, but mechanisms responsible for viral latency are insufficiently clear. Here, we used matched integration site and proviral sequencing (MIP-Seq), an experimental approach involving multiple displacement amplification of individual proviral species, followed by near-full-length HIV-1 next-generation sequencing and corresponding chromosomal integration site analysis to selectively map the chromosomal positions of intact and defective proviruses in 3 HIV-1-infected individuals undergoing long-term antiretroviral therapy. Simultaneously, chromatin accessibility and gene expression in autologous CD4+ T cells were analyzed by assays for transposase-accessible chromatin using sequencing (ATAC-Seq) and RNA-Seq. We observed that in comparison to proviruses with defective sequences, intact HIV-1 proviruses were enriched for non-genic chromosomal positions and more frequently showed an opposite orientation relative to host genes. In addition, intact HIV-1 proviruses were preferentially integrated in either relative proximity to or increased distance from active transcriptional start sites and to accessible chromatin regions. These studies strongly suggest selection of intact proviruses with features of deeper viral latency during prolonged antiretroviral therapy, and may be informative for targeting the genome-intact viral reservoir.