# Yoda1, a Piezo1 agonist, induced latent HIV reactivation associated with upregulation of CD3/TCR complex and HLA genes

## TL;DR

Yoda1, a molecule that activates a cell membrane protein called Piezo1, can awaken dormant HIV, which is a key step toward finding a cure.

## Contribution

Yoda1 is identified as a novel latency-reversing agent for HIV through Piezo1 activation and calcium signaling.

## Key findings

- Yoda1 reactivated latent HIV in both lab-grown cells and patient-derived blood cells.
- Yoda1 increased HIV gene expression and virus production via T cell activation and HLA gene upregulation.
- Transcriptomic and proteomic data revealed a new pathway for HIV reactivation involving host and viral gene regulation.

## Abstract

There is currently no cure for HIV because of the presence of latent viral reservoirs in people with HIV (PWH) on antiretroviral therapy (ART). Latency-reversing agents (LRAs) that can effectively reactivate and destroy latent HIV are being developed as a possible cure for HIV. Here, we identify Yoda1, a Piezo1 agonist, as a novel LRA. Yoda1 reactivated latent HIV in vitro ACH2 cells and ex vivo PBMCs from an HIV patient on ART. Yoda1 induced infectious virus production and HIV gene expression via Piezo1 activation and calcium signaling. Transcriptomic and proteomic analyses revealed a unique latent HIV reactivation pathway involving T cell activation, upregulation of TCR/CD3 and HLA genes, as well as modulation of host and viral transcription and translation that favors viral gene expression. These findings suggest further testing and development of Yoda1 as an effective LRA to reactivate latent HIV and destroy latent reservoirs for the cure of HIV.