HIV VIS Detail Information

> This page shows VIS [4016821] detail information, including site information (chromosome, GRCh38 location, disease, sample, etc) and literature information.

Site Information

DVID	4016821
Chromosome	chr22
GRCh38 Location	49881426
Disease	HIV Infections Acquired Immunodeficiency Syndrome
Target Gene	ZBED4

Literature Information

PubMed PMID	31776247
Year	2019 Dec 17;116(51):25891-25899
Journal	Proceedings of the National Academy of Sciences of the United States of America
Title	Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors.
Author	Patro SC,Brandt LD,Bale MJ,Halvas EK,Joseph KW,Shao W,Wu X,Guo S,Murrell B,Wiegand A,Spindler J,Raley C,Hautman C,Sobolewski M,Fennessey CM,Hu WS,Luke B,Hasson JM,Niyongabo A,Capoferri AA,Keele BF,Milush J,Hoh R,Deeks SG,Maldarelli F,Hughes SH,Coffin JM,Rausch JW,Mellors JW,Kearney MF
Evidence	Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration. We applied this method to lymph node and peripheral blood mononuclear cells from 5 ART-treated donors to determine whether groups of identical subgenomic sequences in the 2 compartments are the result of clonal expansion of infected cells or a viral genetic bottleneck. We found that identical proviral sequences can result from both cellular expansion and viral genetic bottlenecks occurring prior to ART initiation and following ART failure. We identified an expanded T cell clone carrying an intact provirus that matched a variant previously detected by viral outgrowth assays and expanded clones with wild-type and drug-resistant defective proviruses. We also found 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from which we could infer the sequence of the intact parental virus. Thus, MDA-SGS can be used for ""viral reconstruction"" to better understand intrapatient HIV-1 evolution and to determine the clonality and structure of proviruses within expanded clones, including those with drug-resistant mutations. Importantly, we demonstrate that identical sequences observed by standard SGS are not always sufficient to establish proviral clonality.