FUBP3 enhances HIV-1 transcriptional activity and regulates immune response pathways in T cells
Year: 2025
Type: article
Abstract: Far-upstream element-binding protein 3 (FUBP3) was identified at actively transcribing HIV promoters through chromatin affinity purification and mass spectrometry. Known for regulating cellular processes such as transcription and translation by binding to DNAs and RNAs, FUBP3's role in HIV transcriptional regulation was previously unrecognized. This study reveals that FUBP3 enhances HIV-1 transcriptional activation by interacting with Tat and trans-activation response (TAR)-RNA, critical for boosting viral transcription through recruitment of activating factors that promote RNA polymerase II (RNAPII) elongation. Transcriptomic analysis, chromatin immunoprecipitation, and biochemical assays demonstrated that FUBP3 associates with and stabilizes TAR-RNA, in a Tat-dependent manner, and enhances Tat steady-state levels via interaction with Tat's basic domain. Suppressing FUBP3 decreased HIV-1 transcription and altered expression of host genes linked to T cell activation and inflammation, underscoring its broad regulatory impact. Additionally, FUBP3 was enriched at active promoters, confirming its role in transcriptional regulation at specific genomic locations. These findings highlight FUBP3's critical role in the HIV-1 life cycle and suggest its potential as a therapeutic target in HIV-1 infection. Additionally, this study expands our understanding of FUBP3's functions in oncogenic and inflammatory pathways.
Authors: Quentin M.R. Gibaut, Chuan Li, Anqi Cheng, Ines Moranguinho, Luisa P. Mori, Susana T. Valente
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Awards: Identification and characterization of chromatin regulators of HIV-1 latency, G372528187, G3804817475, G3873710400, G4718704777, G4983461495, G5061000936, G5257225330, G7207811988, G7378506915, G7951445289, G8317438145, Host factors regulating HIV latency and reactivation, Evaluation of didehydro-Cortistatin A as a block-and-lock agent for a functional HIV cure in a macaque model
OpenAlex ID: W4408863531