RNA Polymerase III Regulates HIV Replication and Latency.
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Issue Date
2025-09-20
Authors
Thompson, Landon*
Jamal, Imran*
Das, Juthika*
Dang, Casey*
Hong, Zhenzi*
Katz, Doran*
Bosque, Alberto
Singh, Vir B
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Abstract
The elimination of HIV latent reservoirs is an extremely challenging task due to the interplay of multiple mechanisms regulating latency. Thus, we need to identify novel strategies to target heterogeneous reservoirs uniformly. Recent reports have provided intriguing evidence for the novel antiviral function of RNA Polymerase III (RNAP III), which remains to be further explored. In this study, we evaluated the role of RNA Pol III in regulating HIV latency and replication. We first demonstrated that the pharmacological inhibition of RNAP III can lead to a strong reactivation of latency in cell lines representing both T and monocytic cellular reservoirs. Next, we investigated the involvement of RNA Pol III in regulating HIV-1 replication using HIV-1 pseudotyped (DuoFluo) virus and HIV-1-Bal in THP-1 and Sup-T1 cells. We show that the pharmacological inhibition of RNAP III significantly induced HIV transcription. These findings were further confirmed in physiologically relevant primary CD4 T cells, and a consistent increase in HIV transcription was observed up to 72 h. Collectively, our study suggests that inhibition of RNAP III can increase the rate of HIV transcription, while the total HIV DNA remains unchanged. Overall, our study identifies a previously unknown role of RNA Pol III in restricting HIV transcription and advocates that targeting RNAP III-driven mechanisms could be a novel strategy to reactivate HIV latent reservoirs.
Citation
Thompson L, Jamal I, Das J, Dang C, Hong Z, Katz D, Bosque A, Singh VB. RNA Polymerase III Regulates HIV Replication and Latency. Viruses. 2025 Sep 20;17(9):1278. doi: 10.3390/v17091278. PMID: 41012705; PMCID: PMC12474107.
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Grants
R15 AI165295/AI/NIAID NIH HHS/United States , R15 AI165295-01A1/National Institute of Allergy and Infectious Diseases (NIAID)