ArticleRetrovirology2012
HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- The LEDGIN GS-9822 inhibits HIV-2 infection and enhances HIV-2 latency.Microbiology spectrum · 2026Article
- Disruption of LEDGF/p75-directed integration derepresses antisense transcription of the HIV-1 genome.bioRxiv : the preprint server for biology · 2024Article
- Review
- Involvement of Human Cellular Proteins and Structures in Realization of the HIV Life Cycle: A Comprehensive Review, 2024.Viruses · 2024Review
- KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair.International journal of molecular sciences · 2023Article
- GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture.Antimicrobial agents and chemotherapy · 2023Article
- The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder.Biochemical Society transactions · 2023Review
- Characterization of Hepatoma-Derived Growth Factor-Related Protein 2 Interactions with Heterochromatin.Cells · 2023Article
- Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022Review
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors.Viruses · 2022Article
- Article
- Factors that mold the nuclear landscape of HIV-1 integration.Nucleic acids research · 2021Review
- HIV Capsid and Integration Targeting.Viruses · 2021Review
- LEDGINs, Inhibitors of the Interaction Between HIV-1 Integrase and LEDGF/p75, Are Potent Antivirals with a Potential to Cure HIV Infection.Advances in experimental medicine and biology · 2021Article
- Towards a Functional Cure of HIV-1: Insight Into the Chromatin Landscape of the Provirus.Frontiers in microbiology · 2021Review
- A small targeting domain in Ty1 integrase is sufficient to direct retrotransposon integration upstream of tRNA genes.The EMBO journal · 2020Article
- The chromatin landscape at the HIV-1 provirus integration site determines viral expression.Nucleic acids research · 2020Article
- A Peptide Derived from Lens Epithelium-Derived Growth Factor Stimulates HIV-1 DNA Integration and Facilitates Intasome Structural Studies.Journal of molecular biology · 2020Article
- Block-And-Lock Strategies to Cure HIV Infection.Viruses · 2020Review
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7 authors.
Funding
Abstract
backgroundLens epithelium-derived growth factor (LEDGF/p75) is a cellular co-factor of HIV-1 integrase (IN) that tethers the viral pre-integration complex to the host cell chromatin and determines the genome wide integration site distribution pattern of HIV-1. Recently, we demonstrated that HIV-1 replication was reduced in LEDGF/p75 knockout (KO) cells. LEDGF/p75 KO significantly altered the integration site preference of HIV-1, but the pattern remained distinct from a computationally generated matched random control set (MRC), suggesting the presence of an alternative tethering factor. We previously identified Hepatoma-derived growth factor related protein 2 (HRP-2) as a factor mediating LEDGF/p75-independent HIV-1 replication. However, the role of HRP-2 in HIV-1 integration site selection was not addressed.
findingsWe studied the HIV-1 integration site distribution in the presence and absence of LEDGF/p75 and/or HRP-2, and in LEDGF/p75-depleted cells that overexpress HRP-2. We show that HRP-2 functions as a co-factor of HIV-1 IN in LEDGF/p75-depleted cells. Endogenous HRP-2 only weakly supported HIV-1 replication in LEDGF/p75 depleted cells. However, HRP-2 overexpression rescued HIV-1 replication and restored integration in RefSeq genes to wild-type levels. Additional HRP-2 KD in LEDGF/p75-depleted cells reduces integration frequency in transcription units and shifts the integration distribution towards random.
conclusionsWe demonstrate that HRP-2 overexpression can compensate for the absence of LEDGF/p75 and indicate that the residual bias in integration targeting observed in the absence of LEDGF/p75 can be ascribed to HRP-2. Knockdown of HRP-2 upon LEDGF/p75 depletion results in a more random HIV-1 integration pattern. These data therefore reinforce the understanding that LEDGF/p75 is the dominant HIV-1 IN co-factor.
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