ArticleJournal of virology2021
Human Three Prime Repair Exonuclease 1 Promotes HIV-1 Integration by Preferentially Degrading Unprocessed Viral DNA.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- Effect of TAR hairpin stabilization on HIV-1 reverse transcription.Journal of virology · 2026Article
- Research progress on HIV-1 structural proteins and antiviral therapies.Frontiers in immunology · 2026Review
- CPSF6 promotes HIV-1 preintegration complex function.Journal of virology · 2025Article
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- Cyclophilin A facilitates HIV-1 integration.Journal of virology · 2024Article
- Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.Nature communications · 2024Article
- Three Prime Repair Exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural and conformational properties.bioRxiv : the preprint server for biology · 2024Article
- Association of TREX1 polymorphism with disease progression in human immunodeficiency virus type-1 (HIV-1) infected patients.Virus genes · 2023Article
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- HIV-1 Preintegration Complex Preferentially Integrates the Viral DNA into Nucleosomes Containing Trimethylated Histone 3-Lysine 36 Modification and Flanking Linker DNA.Journal of virology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Three prime repair exonuclease 1 (TREX1) is the most abundant 3'→5' exonuclease in mammalian cells. It has been suggested that TREX1 degrades HIV-1 DNA to enable the virus to evade the innate immune system. However, the exact role of TREX1 during early steps of HIV-1 infection is not clearly understood. In this study, we report that HIV-1 infection is associated with upregulation, perinuclear accumulation, and nuclear localization of TREX1. However, TREX1 overexpression did not affect reverse transcription or nuclear entry of the virus. Surprisingly, HIV-1 DNA integration was increased in TREX1-overexpressing cells, suggesting a role of the exonuclease in the post-nuclear entry step of infection. Accordingly, preintegration complexes (PICs) extracted from TREX1-overexpressing cells retained higher levels of DNA integration activity. TREX1 depletion resulted in reduced levels of proviral integration, and PICs formed in TREX1-depleted cells retained lower DNA integration activity. Addition of purified TREX1 to PICs also enhanced DNA integration activity, suggesting that TREX1 promotes HIV-1 integration by stimulating PIC activity. To understand the mechanism, we measured TREX1 exonuclease activity on substrates containing viral DNA ends. These studies revealed that TREX1 preferentially degrades the unprocessed viral DNA, but the integration-competent 3'-processed viral DNA remains resistant to degradation. Finally, we observed that TREX1 addition stimulates the activity of HIV-1 intasomes assembled with the unprocessed viral DNA but not that of intasomes containing the 3'-processed viral DNA. These biochemical analyses provide a mechanism by which TREX1 directly promotes HIV-1 integration. Collectively, our study demonstrates that HIV-1 infection upregulates TREX1 to facilitate viral DNA integration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.