HIV VIS Detail Information

> This page shows VIS [4010141] detail information, including site information (chromosome, GRCh38 location, disease, sample, etc) and literature information.

Site Information

DVID	4010141
VISID	TVIS30000896
Chromosome	chr19
GRCh38 Location	4381104
Disease	HIV infection/AIDS
Sample	Cell line
Virus Reference Genome	Not given
Target Gene	PPP5C

Literature Information

PubMed PMID	28086908
Published year	2017
Journal	Retrovirology
Title	HIV integration sites in latently infected cell lines: evidence of ongoing replication.
Author	Symons J,Chopra A,Malatinkova E,De Spiegelaere W,Leary S,Cooper D,Abana CO,Rhodes A,Rezaei SD,Vandekerckhove L,Mallal S,Lewin SR,Cameron PU
Evidence	BACKGROUND: Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. RESULTS: We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines. Latently infected cell lines infected with intact virus demonstrated multiple distinct HIV integration sites (28 different sites in U1, 110 in ACH-2 and 117 in J1. In contrast, cell lines infected with replication-incompetent viruses (J-Lat cells) demonstrated single integration sites. Following in vitro passaging of the ACH-2 cell line, we observed a significant increase in the frequency of unique HIV integration sites and there were multiple mutations and large deletions in the proviral DNA. When the ACH-2 cell line was cultured with the integrase inhibitor raltegravir, there was a significant decrease in the number of unique HIV integration sites and a transient increase in the frequency of 2-LTR circles consistent with virus replication in these cells. CONCLUSION: Cell lines latently infected with intact HIV demonstrated multiple unique HIV integration sites indicating that these cell lines are not clonal and in the ACH-2 cell line there was evidence of low level virus replication.