ArticleScience advances2023
POLE3 is a repressor of unintegrated HIV-1 DNA required for efficient virus integration and escape from innate immune sensing.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Structural basis of lenacapavir-induced HIV-1 capsid defects during virion maturation.Nature communications · 2026Article
- Proximal proteomics analysis reveals DNA polymerase δ subunit 3 is a new MCM2 binding partner and promotes parental histones inheritance in mammalian cells.Cell death and differentiation · 2026Article
- Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The influence of HIV sense and antisense transcripts on stochastic HIV transcription and reactivation.Computational and structural biotechnology journal · 2025Article
- Involvement of Human Cellular Proteins and Structures in Realization of the HIV Life Cycle: A Comprehensive Review, 2024.Viruses · 2024Review
- PTEN Mediates the Silencing of Unintegrated HIV-1 DNA.Viruses · 2024Article
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
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Abstract
Unintegrated retroviral DNA is transcriptionally silenced by host chromatin silencing factors. Here, we used the proteomics of isolated chromatin segments method to reveal viral and host factors associated with unintegrated HIV-1DNA involved in its silencing. By gene silencing using siRNAs, 46 factors were identified as potential repressors of unintegrated HIV-1DNA. Knockdown and knockout experiments revealed POLE3 as a transcriptional repressor of unintegrated HIV-1DNA. POLE3 maintains unintegrated HIV-1DNA in a repressive chromatin state, preventing RNAPII recruitment to the viral promoter. POLE3 and the recently identified host factors mediating unintegrated HIV-1 DNA silencing, CAF1 and SMC5/SMC6/SLF2, show specificity toward different forms of unintegrated HIV-1DNA. Loss of POLE3 impaired HIV-1 replication, suggesting that repression of unintegrated HIV-1DNA is important for optimal viral replication. POLE3 depletion reduces the integration efficiency of HIV-1. POLE3, by maintaining a repressive chromatin structure of unintegrated HIV-1DNA, ensures HIV-1 escape from innate immune sensing in primary CD4
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