scholarly journals HIV integration site selection: Analysis by massively parallel pyrosequencing reveals association with epigenetic modifications

2007 ◽  
Vol 17 (8) ◽  
pp. 1186-1194 ◽  
Author(s):  
G. P. Wang ◽  
A. Ciuffi ◽  
J. Leipzig ◽  
C. C. Berry ◽  
F. D. Bushman
Keyword(s):  
Site Selection ◽  
Integration Site ◽  
Epigenetic Modifications ◽  
Massively Parallel ◽  
Selection Analysis ◽  
Hiv Integration ◽  
Parallel Pyrosequencing ◽  
Integration Site Selection

scholarly journals Impact of Nucleoporin-Mediated Chromatin Localization and Nuclear Architecture on HIV Integration Site Selection

2015 ◽  
Vol 89 (19) ◽  
pp. 9702-9705 ◽  
Author(s):  
Richard W. Wong ◽  
João I. Mamede ◽  
Thomas J. Hope
Keyword(s):  
Site Selection ◽  
Target Genes ◽  
Integration Site ◽  
Nuclear Architecture ◽  
Underlying Mechanism ◽  
Site Preference ◽  
Nucleocytoplasmic Trafficking ◽  
Integration Sites ◽  
Hiv Integration ◽  
Integration Site Selection

It has been known for a number of years that integration sites of human immunodeficiency virus type 1 (HIV-1) DNA show a preference for actively expressed chromosomal locations. A number of viral and cellular proteins are implicated in this process, but the underlying mechanism is not clear. Two recent breakthrough publications advance our understanding of HIV integration site selection by focusing on the localization of the preferred target genes of integration. These studies reveal that knockdown of certain nucleoporins and components of nucleocytoplasmic trafficking alter integration site preference, not by altering the trafficking of the viral genome but by altering the chromatin subtype localization relative to the structure of the nucleus. Here, we describe the link between the nuclear basket nucleoporins (Tpr and Nup153) and chromatin organization and how altering the host environment by manipulating nuclear structure may have important implications for the preferential integration of HIV into actively transcribed genes, facilitating efficient viral replication.

scholarly journals Insight in HIV Integration Site Selection Provides a Block-and-Lock Strategy for a Functional Cure of HIV Infection

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 12 ◽  
Author(s):  
Zeger Debyser ◽  
Gerlinde Vansant ◽  
Anne Bruggemans ◽  
Julie Janssens ◽  
Frauke Christ
Keyword(s):  
Hiv Infection ◽  
Site Selection ◽  
Integration Site ◽  
Viral Reservoir ◽  
Dependent Manner ◽  
Functional Cure ◽  
Infected Cells ◽  
Hiv Integration ◽  
Integration Site Selection

Despite significant improvements in therapy, the HIV/AIDS pandemic remains an important threat to public health. Current treatments fail to eradicate HIV as proviral DNA persists in long-living cellular reservoirs, leading to viral rebound whenever treatment is discontinued. Hence, a better understanding of viral reservoir establishment and maintenance is required to develop novel strategies to destroy latently infected cells, and/or to durably silence the latent provirus in infected cells. Whereas the mechanism of integration has been well studied from a catalytic point of view, it remains unknown how integration site selection and transcription are linked. In recent years, evidence has grown that lens epithelium-derived growth factor p75 (LEDGF/p75) is the main determinant of HIV integration site selection and that the integration site affects the transcriptional state of the provirus. LEDGINs have been developed as small molecule inhibitors of the interaction between LEDGF/p75 and integrase. Recently, it was shown that LEDGIN treatment in cell culture shifts the residual integrated provirus towards the inner nuclear compartment and out of transcription units in a dose dependent manner. This LEDGIN-mediated retargeting increased the proportion of provirus with a transcriptionally silent phenotype and the residual reservoir proved refractory to reactivation in vitro. LEDGINs provide us with a research tool to study the link between integration and transcription, a quintessential question in retrovirology. LEDGIN-mediated retargeting of the residual reservoirs provides a novel potential “block-and-lock” strategy as a functional cure of HIV infection.

scholarly journals HIV Integration Site Selection: Targeting in Macrophages and the Effects of Different Routes of Viral Entry

2006 ◽  
Vol 14 (2) ◽  
pp. 218-225 ◽  
Author(s):  
Stephen D. Barr ◽  
Angela Ciuffi ◽  
Jeremy Leipzig ◽  
Paul Shinn ◽  
Joseph R. Ecker ◽  
...  
Keyword(s):  
Viral Entry ◽  
Site Selection ◽  
Integration Site ◽  
Hiv Integration ◽  
Integration Site Selection

scholarly journals GS-9822, a Preclinical LEDGIN Candidate, Displays a Block-and-Lock Phenotype in Cell Culture

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Anne Bruggemans ◽  
Gerlinde Vansant ◽  
Mini Balakrishnan ◽  
Michael L. Mitchell ◽  
Ruby Cai ◽  
...  
Keyword(s):  
Site Selection ◽  
Integration Site ◽  
Binding Pocket ◽  
Epigenetic Landscape ◽  
Functional Cure ◽  
Cellular Cofactor ◽  
Integration Sites ◽  
First Time ◽  
Hiv Integration ◽  
Integration Site Selection

ABSTRACT The ability of HIV to integrate into the host genome and establish latent reservoirs is the main hurdle preventing an HIV cure. LEDGINs are small-molecule integrase inhibitors that target the binding pocket of LEDGF/p75, a cellular cofactor that substantially contributes to HIV integration site selection. They are potent antivirals that inhibit HIV integration and maturation. In addition, they retarget residual integrants away from transcription units and toward a more repressive chromatin environment. As a result, treatment with the LEDGIN CX14442 yielded residual provirus that proved more latent and more refractory to reactivation, supporting the use of LEDGINs as research tools to study HIV latency and a functional cure strategy. In this study, we compared GS-9822, a potent, preclinical lead compound, with CX14442 with respect to antiviral potency, integration site selection, latency, and reactivation. GS-9822 was more potent than CX14442 in most assays. For the first time, the combined effects on viral replication, integrase-LEDGF/p75 interaction, integration sites, epigenetic landscape, immediate latency, and latency reversal were demonstrated at nanomolar concentrations achievable in the clinic. GS-9822 profiles as a preclinical candidate for future functional cure research.

scholarly journals MLV integration site selection is driven by strong enhancers and active promoters

2014 ◽  
Vol 42 (7) ◽  
pp. 4257-4269 ◽  
Author(s):  
Matthew C. LaFave ◽  
Gaurav K. Varshney ◽  
Derek E. Gildea ◽  
Tyra G. Wolfsberg ◽  
Andreas D. Baxevanis ◽  
...  
Keyword(s):  
Site Selection ◽  
Integration Site ◽  
Integration Site Selection

scholarly journals 734. The Influence of Vector Design on Integration Site Selection by gamma-Retroviral and Lentiviral Vectors

2006 ◽  
Vol 13 ◽  
pp. S284
Author(s):  
Alessandra Recchia ◽  
Claudia Cattoglio ◽  
Annarita Miccio ◽  
Antonella Antonelli ◽  
Anna Testa ◽  
...  
Keyword(s):  
Site Selection ◽  
Integration Site ◽  
Lentiviral Vectors ◽  
Integration Site Selection

scholarly journals Convergent evolution of integration site selection upstream of tRNA genes by yeast and amoeba retrotransposons

2018 ◽  
Vol 46 (14) ◽  
pp. 7250-7260 ◽  
Author(s):  
Eva Kling ◽  
Thomas Spaller ◽  
Jana Schiefner ◽  
Doreen Bönisch ◽  
Thomas Winckler
Keyword(s):  
Site Selection ◽  
Convergent Evolution ◽  
Integration Site ◽  
Trna Genes ◽  
Integration Site Selection
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