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Updated: Jun 13, 2026

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
Identification of the cellular factor KLF16 as a novel epigenetic repressor of HIV-1 transcription
Carine Van Lint1, Marion Santangelo1, Maryam Bendoumou1
1Service of Molecular Virology, Department of Molecular Biology (DBM), Université libre de Bruxelles (ULB), Gosselies 6041, Belgium.
Abstract:
Despite antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) persists in latently-infected cells through epigenetic and transcriptional mechanisms. Latency-reversing agents have failed clinically, partly due to incomplete understanding of HIV-1 latency reversal. Here, using DNA-affinity capture and mass spectrometry on the HIV-1 5' long terminal repeat (5'LTR) enhancer-core promoter, we identify KLF16 (Krüppel-like Factor 16) as a novel regulator of HIV-1 gene expression. KLF16 binds to the HIV-1 5'LTR in vivo at Sp1 binding sites, and KLF16 depletion reactivates latent HIV-1 in T-lymphoid and monocytic cell models. Mechanistically, KLF16 represses HIV-1 transcription by competing with Sp1 for promoter binding and by recruiting the Sin3A/HDAC1 and HP1α/Suv39H1 repressive epigenetic complexes. KLF16 is also upregulated in CD4+ T cells from ART-treated people with HIV-1 upon T-cell activation. Additionally, All-Trans retinoic acid (ATRA) reactivates latent HIV-1 in myeloid cells, partly by downregulating KLF16. These findings establish KLF16 as a novel transcriptional repressor of HIV-1, identifying it as a potential promising therapeutic target for cure strategies.
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