A new HIV-1 latency reversing agent activating HIV-Tat
Abstract
Despite its efficiency to prevent viral multiplication, antiretroviral therapy does not affect HIV-1 latently-infected cells. These cells do not produce significant amounts of viruses and constitute HIV-1 reservoir. To purge this long-lived viral reservoir, the "shock and kill" strategy relies on the use of latency reversing agents (LRAs) to induce activation of latent cells. All LRAs developed until now target cellular proteins and are therefore not specific for HIV-infected cells. Here we present a new LRA that binds and activates HIV-1 Tat which is the key regulator for viral transcription and latency reversal. This molecule termed D10 was designed to bind to the major groove of the Tat protein, and found to activate Tat transcriptional activity by stabilizing the HIV transcription complex. This LRA induces strong HIV production by latent cell lines and latent cells from people living with HIV-1. On latent cells from PBMCs, D10 is active at ∼50 nM, the concentration required to stabilize HIV transcription complex. D10 is the first Tat activator available and the first LRA that targets an HIV protein.
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BibTeX
@misc{tong2026hiv1,
title = {{A new HIV-1 latency reversing agent activating HIV-Tat}},
author = {Phuoc Bao Viet Tong and Laetitia Marty and Nawel Chekrit and Martine Pugnière and Jean-Marie Péloponèse and Célia Bouhnik and Edouard Tuaillon and Alain Makinson and Laurent Chaloin and Bruno Beaumelle},
howpublished = {HAL},
year = {2026},
month = aug,
doi = {10.64898/2026.08.20.745916},
url = {https://hal.science/hal-05767151v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A new HIV-1 latency reversing agent activating HIV-Tat
AU - Phuoc Bao Viet Tong
AU - Laetitia Marty
AU - Nawel Chekrit
AU - Martine Pugnière
AU - Jean-Marie Péloponèse
AU - Célia Bouhnik
AU - Edouard Tuaillon
AU - Alain Makinson
AU - Laurent Chaloin
AU - Bruno Beaumelle
PY - 2026
DA - 2026/08/21
PB - HAL
DO - 10.64898/2026.08.20.745916
UR - https://hal.science/hal-05767151v1
AB - Despite its efficiency to prevent viral multiplication, antiretroviral therapy does not affect HIV-1 latently-infected cells. These cells do not produce significant amounts of viruses and constitute HIV-1 reservoir. To purge this long-lived viral reservoir, the "shock and kill" strategy relies on the use of latency reversing agents (LRAs) to induce activation of latent cells. All LRAs developed until now target cellular proteins and are therefore not specific for HIV-infected cells. Here we present a new LRA that binds and activates HIV-1 Tat which is the key regulator for viral transcription and latency reversal. This molecule termed D10 was designed to bind to the major groove of the Tat protein, and found to activate Tat transcriptional activity by stabilizing the HIV transcription complex. This LRA induces strong HIV production by latent cell lines and latent cells from people living with HIV-1. On latent cells from PBMCs, D10 is active at ∼50 nM, the concentration required to stabilize HIV transcription complex. D10 is the first Tat activator available and the first LRA that targets an HIV protein.
ER -