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Original Research Open Access

TGF-β Suppresses HIV-1 Reactivation in U1 Cells by Reducing NFAT, Sp1, and TF Levels while Enhancing Bcl-xL

  • 1Lab of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration. Silver Spring, MD 20993, USA
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Corresponding Author

Xue Wang, xue.wang@fda.hhs.gov

Received Date: July 01, 2026

Accepted Date: August 13, 2026

Abstract

TGF-β plays an important role in keeping HIV-1 in a hidden, inactive state by suppressing the immune system and creating conditions that prevent the virus from reactivating. However, exactly how TGF-β does this is not well understood. In this study, we used the U1 cell line to explore how TGF-β affects HIV-1 reactivation. We used real-time PCR and Western blotting to measure changes in viral activity and related cell pathways. We found that cells expressing TGF-β had lower levels of HIV-1 RNA compared to control cells. This effect appears to be due to TGF-β lowering the levels of certain host transcription factors like NFAT and Sp1, which are needed for activating HIV-1, while having no effect on AP-1 and NF-κBp65. TGF-β also blocks pathways like P-TEFb and Jak/Stat, which are important for turning on and copying HIV-1 genes. In addition, TGF-β reduces cell death by blocking both main types of apoptosis pathways and increasing Bcl-xL levels, which help cells survive. Together, these effects help HIV-1 stay inactive and hidden in the body. This makes it harder to cure HIV because the virus can remain in a dormant state. Our results suggest that targeting TGF-β could help develop new treatments to wake up and remove hidden HIV-1. Understanding how TGF-β controls HIV-1 latency and cell survival may help improve strategies to fully eliminate the virus.

Keywords

HIV-1, Latency, TGF-β, Transcription factor, Apoptosis, Bcl-xL

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